heptane-1,7-diamine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,7-Diaminoheptane (5.2 g) was warmed gently until molten and to it was added N-cyano-N'-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]-S-methylisothiourea (2.69 g). After stirring for 15 hours at room temperature the reaction mixture was extracted with ether to remove excess of the diamine starting material and then purified on a silica gel chromatographic column, eluting with isopropanol to give the title compound (1.08 g), m.p. 84°-87° C. was extracted with ether to remove excess of the diamine starting material purified on a silica gel chromatographic column eluting with isopropanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,7-Diaminoheptane (5.2 g) was warmed gently until molten and to it was added N-cyano-N'-[2-((4-methyl-5-imidazolyl)-methylthio)ethyl]-S-methylisothiourea (2.69 g). After stirring for 15 hours at room temperature the reaction mixture was extracted with ether to remove excess of the diamine starting material and then purified on a silica gel chromatographic column, eluting with isopropanol to give the title compound (1.08 g), m.p. 84°-87° C. (Found: C, 55.0; H, 8.2; N, 27.8; S, 9.0% C16H29N7S requires: C, 54.7; H, 8.3; N, 27.9; S, 9.1%). was extracted with ether to remove excess of the diamine starting material purified on a silica gel chromatographic column eluting with isopropanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Combine 1,7-diaminoheptane (65.0 g, 0.5 mol), benzaldehyde (106 gm, 1 mol) and platinum oxide (PtO2)[2.0 g] in ethanol (800 ml) and treat the mixture with hydrogen gas (45 lb/in2) until the uptake of gas ceases. Remove the catalyst by filtration and remove the solvent in vacuo. Purify the residue by bulb to bulb distillation to yield 99.4 g of the title compound (bp 191°-195° C. @1.0 mm/Hg). Remove the catalyst by filtration remove the solvent in vacuo Purify the residue by bulb to bulb distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared in analogy to Example 3-1 in Scheme 5 by using 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (prepared in analogy to the one in Example 2-1) and heptane-1,7-diamine. MS obsd. (ESI+) [(M+H)+] 467, 1H NMR (400 MHz, CD3OD) δ ppm 8.07 (dd, J=1.2, 0.8 Hz, 1 H), 7.97 (s, 1 H), 7.92 (d, J=7.6 Hz, 1 H), 7.74-7.68 (m, 2 H), 7.61-7.56 (m, 2 H), 5.91 (s, 1 H), 5.32 (s, 2 H), 4.52 (brs, 2 H), 3.75 (d, J=4.80 Hz, 2 H), 3.31 (d, J=1.60 Hz, 2 H), 2.94 (m, 2 H), 2.45 (s, 3 H), 1.72 (m, 4 H), 1.50 (m, 6 H).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: On an ice-water bath, to the solution of 1,7-diaminoheptane (1.433 g, 11 mmol) in CH2Cl2/MeOH (125 mL/125 mL) was added the solution of CbzCl (1.71 g, 10 mmol) in CH2Cl2 (250 mL) dropwise within 12 h while keeping the temperature below 5° C. The mixture was allowed to stir at the same temperature for another half of an hour before concentrated under reduced pressure to remove most of the MeOH. Water (150 mL) was then added, and the aqueous layer was adjusted to pH=2 using 6 N HCl. The layers were separated. The aqueous layer was washed with DCM (50 mL×3), then adjusted to pH=12 with 10 N NaOH and extracted with DCM (50 mL×3). The combined organic layers were dried over Na2SO4, concentrated and purified by flash column using DCM/MeOH (9/1) to give 856 mg white solid in 32% yield. 1H NMR (400 MHz, CDCl3): δ7.35-7.29 (m, 5H), 5.09 (s, 2H), 4.73 (brs, 1H), 3.18 (q, J=6.64 Hz, 2H), 2.67 (t, J=6.94 Hz, 2H), 1.55-1.44 (m, 2H), 1.44-1.40 (m, 2H), 1.32 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 156.40, 136.70, 128.50, 128.09, 128.06, 66.55, 42.18, 41.06, 33.71, 29.91, 29.09, 26.76, 26.68. mp 78-80° C. IR v (Diamond, cm−1): 3327, 1686, 1532, 1263, 1144. MS (ESI) m/z found 264.8 (M+H)+. the temperature below 5° C before concentrated under reduced pressure to remove most of the MeOH Water (150 mL) was then added The layers were separated The aqueous layer was washed with DCM (50 mL×3) extracted with DCM (50 mL×3) The combined organic layers were dried over Na2SO4 concentrated purified by flash column

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The intermediate N,N'-di-n-propyl-1,7-heptanediamine was prepared as follows: To a solution containing 43.5 g. of pyridine in 600 ml. of benzene cooled in an ice bath was added dropwise over a period of 10 minutes 51.0 g. of propionyl chloride. To the resulting stirred and cooled solution was added dropwise over a period of 30 minutes 32.5 g. of 1,7-heptanediamine. After the ice bath was removed, the reaction mixture was stirred at room temperature for 20 hours and then filtered to remove a pale yellow solid. The filtrate was evaporated in vacuo. The residual material was combined with the pale yellow solid and the mixture was shaken well with a mixture of 500 ml. of chloroform, 500 ml. of water and 10 ml. of 12N hydrochloric acid. The layers were separated and the acidic aqueous layer was extracted with four 150 ml. portions of chloroform. The combined chloroform extracts were dried over anhydrous potassium carbonate. When the solid separated from the chloroform solution, an additional 750 ml. of chloroform was added. The mixture was heated to boiling and filtered through a sintered glass funnel. The chloroform solution was evaporated in vacuo and the solid residue was recrystallized from 250 ml. of acetonitrile and dried in a vacuum oven at 50° C. to yield 43.1 g. of heptamethylenebis(propionamide), m.p. 132°-133.5° C. To a solution containing 43.5 g was added dropwise over a period of 10 minutes 51.0 g cooled solution was added dropwise over a period of 30 minutes 32.5 g After the ice bath was removed the reaction mixture was stirred at room temperature for 20 hours filtered to remove a pale yellow solid The filtrate was evaporated in vacuo the mixture was shaken well with a mixture of 500 ml The layers were separated the acidic aqueous layer was extracted with four 150 ml The combined chloroform extracts were dried over anhydrous potassium carbonate When the solid separated from the chloroform solution of chloroform was added The mixture was heated filtered through a sintered glass funnel The chloroform solution was evaporated in vacuo the solid residue was recrystallized from 250 ml of acetonitrile and dried in a vacuum oven at 50° C. to yield 43.1 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: m.p. 181°-182° C., 25.8 g., was prepared as in Example 1 using 4-methylthiobenzoyl chloride (prepared from 31 g. of 4-methylthiobenzoic acid as in Example 6) in 100 ml. of ethylene dichloride, 11.9 g. of 1,7-heptanediamine, 200 ml. of 10% aqueous potassium hydroxide solution, 500 ml. of ethylene dichloride and recrystallization from acetic acid. of ethylene dichloride and recrystallization from acetic acid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: m.p. 181°-182° C., 25.8 g., was prepared as in Example 1 using 4-methylthiobenzoyl chloride (prepared from 31 g. of 4-methylthiobenzoic acid as in Example 6) in 100 ml. of ethylene dichloride, 11.9 g. of 1,7-heptanediamine, 200 ml. of 10% aqueous potassium hydroxide solution, 500 ml. of ethylene dichloride and recrystallization from acetic acid. of ethylene dichloride and recrystallization from acetic acid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: m.p. 164°-165° C., 9.9 g., was prepared as in Example 23 using 12.0 g. of 4-phenoxybenzoyl chloride (from 16.0 g. of 4-phenoxybenzoic acid as in Example 6) in 20 ml. of ethylene dichloride, 3.8 g. of 1,7-heptanediamine, 40 ml. of ethylene dichloride, 6.9 g. of potassium carbonate, 63 ml. of water and recrystallization from ethylene dichloride. , was prepared as in Example 23 using 12.0 g of water and recrystallization from ethylene dichloride