1,2-Dichloroethane → (S,S)-3-[2-(3-Acetylamino-2-oxo-2H-pyridin-1-yl)-butyrylamino]-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester

HRID 2422689Notes

Reaction equation

HRID 2422689 reaction equation
[C:1]([NH:4][C:5]1[C:6](=[O:17])[N:7]([C@@H:11]([CH2:15][CH3:16])[C:12]([OH:14])=O)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].[C:18]([O:22][C:23](=[O:41])[CH2:24][CH:25]([NH2:40])[CH:26]([OH:39])[CH2:27][O:28][C:29]1[C:34]([F:35])=[C:33]([F:36])[CH:32]=[C:31]([F:37])[C:30]=1[F:38])([CH3:21])([CH3:20])[CH3:19].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C1C=CN=CC=1)C.C1COCC1>[C:18]([O:22][C:23](=[O:41])[CH2:24][C@H:25]([NH:40][C:12](=[O:14])[CH:11]([N:7]1[CH:8]=[CH:9][CH:10]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[C:6]1=[O:17])[CH2:15][CH3:16])[C@H:26]([OH:39])[CH2:27][O:28][C:29]1[C:30]([F:38])=[C:31]([F:37])[CH:32]=[C:33]([F:36])[C:34]=1[F:35])([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 44604219(S)-2-(3-Acetylamino-2-oxo-2H-pyridin-1-yl)-butyric acidHCID 750793883-Amino-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester

Product 1

HCID 86595207(S,S)-3-[2-(3-Acetylamino-2-oxo-2H-pyridin-1-yl)-butyrylamino]-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl esterYield 92%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A stirred mixture of (S)-2-(3-Acetylamino-2-oxo-2H-pyridin-1-yl)-butyric acid (100 mg, 0.42 mmol), 3-amino-5-(2,3,5,6-tetrafluorophenoxy)-4-hydroxy-pentanoic acid tert-butyl ester (163 mg, 0.462 mmol), HOBt (62 mg, 0.462 mmol), DMAP (56 mg, 0.462 mmol) and THF (5 mL) was cooled to 0° C. then EDC (89 mg, 0.462 mmol) was added. The mixture was allowed to warm to room temperature during 16 h then concentrated under reduced pressure. The residue was purified by flash chromatography (50-50% ethyl acetate/hexane) to afford the title compound as a white foam (221 mg, 92%); 1H NMR (400 MHz, CDCl3) δ 0.88-0.93 (3H, m), 1.37-1.38 (9H, 2 s), 1.86-1.96 (1H, m), 2.15-2.25 (4H, m), 2.55-2.71 (2H, m), 3.70-4.64 (5H, m), 5.30-5.39 (1H, m), 6.30-6.35 (1H, m), 6.75-6.86 (1H, m), 7.17-7.31 (2H, m), 8.31-8.47 (2H, m).

Workup

  1. temperatureto warm to room temperature during 16 h
  2. concentrationthen concentrated under reduced pressure
  3. customThe residue was purified by flash chromatography (50-50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-ef5e6603f5e94ec984628ce28b84d4fe
Source dataset
uspto-grants-2011_06
Patent number
US07960415B2

Reaction notes

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