Ammonium Chloride → (R)-2-(5-amino-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyridin-2-ylamino)-2-(4-fluorophenyl)ethanol

HRID 1092243Notes

Reaction equation

[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15]([N+:16]([O-])=O)=[CH:14][N:13]=[C:12]([NH:19][C@H:20]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[CH2:21][OH:22])[CH:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[Cl-].[NH4+].C([O-])(=O)C.[NH4+]>CO.C1COCC1.[Zn]>[NH2:16][C:15]1[C:10]([NH:9][C:6]2[CH:5]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[NH:8][N:7]=2)=[CH:11][C:12]([NH:19][C@H:20]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:21][OH:22])=[N:13][CH:14]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a suspension of (R)-2-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-nitropyridin-2-ylamino)-2-(4-fluorophenyl)ethanol (Method 94, 0.14 g, 0.36 mmol) and zinc dust (0.12 g, 1.78 mmol) in MeOH-THF (1:1, 16 ml) was slowly added saturated ammonium chloride (2.0 ml). The reaction mixture was stirred at 25° C. for 1 hour, to which was then added saturated ammonium acetate solution (5 ml). The resulting mixture was stirred for another 30 minutes. The Zn dust was removed by filtration and washed with EtOAc (20 ml). The organic layer was separated, washed with brine (10 ml), dried over sodium sulfate, and concentrated. The crude product was used directly for the next step without further purification. MS: Calcd.: 368; Found: [M+H]+ 369.

Workup

stirringThe resulting mixture was stirred for another 30 minutes
customThe Zn dust was removed by filtration
washwashed with EtOAc (20 ml)
customThe organic layer was separated
washwashed with brine (10 ml)
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe crude product was used directly for the next step without further purification

Sources & evidence

ORD record: ord-53c5033a2bc844f589975d1201c0de6f
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129403B2

Reaction notes

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