1,2-Dichloroethane → 7-[(3R)-3-[(1,1-Dimethylethoxycarbonyl)amino]-4-(2,5-difluorophenyl)butanoyl]-2-(ethylthio)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine

HRID 1272383Notes

Reaction equation

HRID 1272383 reaction equation
Cl.[CH2:2]([S:4][C:5]1[N:6]=[CH:7][C:8]2[CH2:14][CH2:13][NH:12][CH2:11][C:9]=2[N:10]=1)[CH3:3].[CH3:15][C:16]([CH3:36])([O:18][C:19]([NH:21][C@H:22]([CH2:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[F:35])[CH2:23][C:24](O)=[O:25])=[O:20])[CH3:17].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>ClCCl>[CH3:17][C:16]([CH3:36])([O:18][C:19]([NH:21][C@H:22]([CH2:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[F:35])[CH2:23][C:24]([N:12]1[CH2:13][CH2:14][C:8]2[CH:7]=[N:6][C:5]([S:4][CH2:2][CH3:3])=[N:10][C:9]=2[CH2:11]1)=[O:25])=[O:20])[CH3:15]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11347588(R)-b-(Boc-amino)-2,5-difluorobenzenebutanoic acidHCID 184565142-(Ethylthio)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine hydrochloride

Product 1

HCID 690254087-[(3R)-3-[(1,1-Dimethylethoxycarbonyl)amino]-4-(2,5-difluorophenyl)butanoyl]-2-(ethylthio)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidineYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 47 mg (0.19 mmol) of 2-(ethylthio)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine hydrochloride, 59 mg (0.19 mmol) of (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,5-difluorophenyl)butanoic acid, 37 mg (0.19 mmol) of EDC, 26 mg (0.19 mmol) of HOBt, and 0.15 mL (0.57 mmol) of diisopropylethylamine in 1.5 mL of dichloromethane was stirred at ambient temperature overnight. The mixture was subjected directly to purification by flash chromatography (5 g silica gel cartridge, 20-to-50% ethyl acetate/hexane step gradient) to give 85 mg (91%) of the title compound as a white solid.

Workup

  1. customThe mixture was subjected directly to purification by flash chromatography (5 g silica gel cartridge, 20-to-50% ethyl acetate/hexane step gradient)

Sources & evidence

ORD record
ord-e12eef5478f64e57aa74365249330e0b
Source dataset
uspto-grants-2007_04
Patent number
US07208498B2

Reaction notes

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