tert-butyl (2S)-2-amino-3-[(2-methylpropan-2-yl)oxy]propanoate

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

実験手順: The product from Example 35, Step A, 5-(5,6-difluoro-1H-indol-2-yl)-2-methoxy-phenyl isothiocyanate (0.316 g, 1.0 mmol) was reacted with serine tert-butylether tert-butylester (0.226 g, 1.0 mmol) according to the procedure for Example 23, Step B to give the product after filtration through silica gel using hexanes/ethyl acetate, 1/1, v/v as eluant (0.377 g in 2 portions), mp 111-114° C. to give the product after filtration through silica gel

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 by condensing H-Ser(But)OBut with the protected dipeptide of Example 88, followed by deprotection and purification by HPLC (40%): (Pos. FAB)? (MH+). followed by deprotection and purification by HPLC (40%)

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

実験手順: The product from Example 35, Step A, 5-(5,6-difluoro-1H-indol-2-yl)-2-methoxy-phenyl isothiocyanate (0.316 g, 1.0 mmol) was reacted with serine tert-butylether tert-butylester (0.226 g, 1.0 mmol) according to the procedure for Example 23, Step B to give the product after filtration through silica gel using hexanes/ethyl acetate, 1/1, v/v as eluant (0.377 g in 2 portions), mp 111-114° C. to give the product after filtration through silica gel

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

実験手順: The product from Example 35, Step A, 5-(5,6-difluoro-1H-indol-2-yl)-2-methoxy-phenyl isothiocyanate (0.316 g, 1.0 mmol) was reacted with serine tert-butylether tert-butylester (0.226 g, 1.0 mmol) according to the procedure for Example 23, Step B to give the product after filtration through silica gel using hexanes/ethyl acetate, 1/1, v/v as eluant (0.377 g in 2 portions), mp 111-114° C. to give the product after filtration through silica gel

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (2R)-{[(Benzyloxy)carbonyl]amino}(phenyl)acetic acid (Z-(R)-Phg-OH) (2.0 g, 7.0 mmol) and tert-butyl O-(tert-butyl)-L-serinate (2.0 g, 7.9 mmol) and 2.6-lutidine were dissolved in DCM (30 ml). After stirring 5 minutes at 0° C. TBTU (2.5 g, 7.8 mmol) was added and stirring was continued 30 minutes at 0° C. and 4 hours at room temperature. The reaction mixture was washed with water (2×100 ml), dried and purified with flash chromatography (DCM) to give the title compound (3.3 g, 97%). NMR (300 MHz, CD3OD): 1.05 (s, 9H), 1.45 (s, 9H), 3.4-3.8 (m, 2H), 4.5 (bs, 1H), 4.85 (s, 2H), 5.1 (s, 2H), 5.4 (s, 1H), 7.25-7.5 (m, 10 H). stirring was continued 30 minutes at 0° C. and 4 hours at room temperature The reaction mixture was washed with water (2×100 ml) dried purified with flash chromatography (DCM)

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 by condensing H-Ser(But)OBut with the protected dipeptide of Example 88, followed by deprotection and purification by HPLC (40%): (Pos. FAB) ? (MH+). followed by deprotection and purification by HPLC (40%)

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 by condensing H-Ser(But)OBut with the protected dipeptide of Example 88, followed by deprotection and purification by HPLC (40%): (Pos. FAB) ? (MH+). followed by deprotection and purification by HPLC (40%)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9.07 ml of N-ethylmorpholine and 16.05 g of DCC are added at 0° C. to a solution of 21.2 g of Z-D-Phe-OH, 9.6 g of HOBt and 17.9 g of HCl.H-Ser(tBu)-OtBu in 150 ml of dimethylformamide. The mixture is left to stir at 0° C. for one hour and to stand at room temperature overnight. The precipitate is filtered off with suction, and the filtrate is concentrated. The residue is partitioned between ethyl acetate and water. The ethyl acetate phase is extracted by shaking successively with saturated NaHCO3 solution, KHSO4 /K2SO4 solution and water, dried over Na2SO4 and concentrated. The substance crystallizes after trituration with petroleum ether. The mixture is left to stand at room temperature overnight The precipitate is filtered off with suction the filtrate is concentrated The residue is partitioned between ethyl acetate and water The ethyl acetate phase is extracted by shaking successively with saturated NaHCO3 solution, KHSO4 /K2SO4 solution and water dried over Na2SO4 concentrated The substance crystallizes after trituration with petroleum ether

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

実験手順: The product from Example 100 (56 mg, 0.1 mmole) and H-Ser(tBu)-OtBu (51 mg, 0.2 mmole) were processed as in Example 213A-B to provide the title compound. 1H NMR (500 MHz, DMSO-d6) δ11.72-13.24 (br.s, 1 H), 8.95 (s, 1 H), 8.28-8.51 (br.s, 1 H), 7.91 (d, 1 H), 7.26 (m, 6 H), 7.19 (m, 3 H), 7.04 (m, 1 H), 6.96 (m, 2 H), 6.88 (m, 4 H), 4.27 (m, 1 H), 4.06 (s, 2 H), 4.02 (s, 2 H), 3.64 (m, 2 H), 2.91 (s, 3 H), 2.56 (m, 2 H), 2.39 (s, 3 H), 2.17 (m, 2 H), 1.78 (m, 2 H); MS (APCI+) m/z 646 (M+H)+.

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 by condensing H-Ser(But)OBut with the protected dipeptide of Example 88, followed by deprotection and purification by HPLC (40%): (Pos. FAB)? (MH+). followed by deprotection and purification by HPLC (40%)