Ammonium Chloride → (R)-2-(4-Amino-3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,6-difluorophenylamino)-2-(4-fluorophenyl)ethanol

HRID 1092254Notes

Reaction equation

[Cl-].[NH4+].[CH:3]1([C:6]2[NH:10][N:9]=[C:8]([NH:11][C:12]3[C:13]([F:33])=[C:14]([NH:22][C@H:23]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)[CH2:24][OH:25])[C:15]([F:21])=[CH:16][C:17]=3[N+:18]([O-])=O)[CH:7]=2)[CH2:5][CH2:4]1.C([O-])(=O)C.[NH4+]>CO.C1COCC1.[Zn]>[NH2:18][C:17]1[CH:16]=[C:15]([F:21])[C:14]([NH:22][C@H:23]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH2:24][OH:25])=[C:13]([F:33])[C:12]=1[NH:11][C:8]1[CH:7]=[C:6]([CH:3]2[CH2:5][CH2:4]2)[NH:10][N:9]=1

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of saturated ammonium chloride (4 ml) was added slowly to a suspension (R)-2-(3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,6-difluoro-4-nitrophenylamino)-2-(4-fluorophenyl)ethanol (Method 105, 0.250 g, 0.577 mmol) and zinc dust (0.189 g, 2.88 mmol) in MeOH/THF (10 ml, 1:1). The mixture was stirred at 25° C. for 5 minutes. Saturated ammonium acetate solution (5 ml) was added and the mixture was stirred for another 30 minutes. Zn dust was removed by filtration and the cake was washed with EtOAc (15 ml). The organic layer was separated and dried over sodium sulfate. After removal of solvent, the product was used directly for the next step without further purification.

Workup

stirringthe mixture was stirred for another 30 minutes
customZn dust was removed by filtration
washthe cake was washed with EtOAc (15 ml)
customThe organic layer was separated
dry with materialdried over sodium sulfate
customAfter removal of solvent
customthe product was used directly for the next step without further purification

Sources & evidence

ORD record: ord-0d3be8aaa4c84d719d1fd93929986331
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129403B2

Reaction notes

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