Ammonium Chloride → (S)-2-amino-3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(1-(4-fluorophenyl)ethylamino)benzonitrile

HRID 1092246Notes

Reaction equation

[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:11]([N+:28]([O-])=O)=[C:12]([CH:15]=[C:16]([NH:18][C@H:19]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH3:20])[CH:17]=3)[C:13]#[N:14])[CH:5]=2)[CH2:3][CH2:2]1.[Cl-].[NH4+].C([O-])(=O)C.[NH4+]>CO.C1COCC1.[Zn]>[NH2:28][C:11]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:17][C:16]([NH:18][C@H:19]([C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)[CH3:20])=[CH:15][C:12]=1[C:13]#[N:14]

Participants

Conditions

Temperature: 25 °C

Procedure

To a suspension of (S)-3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(1-(4-fluorophenyl)ethylamino)-2-nitrobenzonitrile (Method 97, 4.20 g, 10.0 mmol) and zinc dust (3.40 g, 52 mmol) in MeOH-THF (1:1, 100 ml) was slowly added saturated ammonium chloride (40 ml). The reaction mixture was stirred at 25° C. for 1 hour, to which was then added saturated ammonium acetate solution (50 ml). The resulting mixture was stirred for another 30 minutes. Zn dust was removed by filtration and washed with EtOAc (200 ml). The organic layer was separated, washed with brine (100 ml), dried over sodium sulfate, and concentrated. The crude product was used directly for the next step without further purification. MS: Calcd: 376; Found: [M+H]+ 377.

Workup

stirringThe resulting mixture was stirred for another 30 minutes
customZn dust was removed by filtration
washwashed with EtOAc (200 ml)
customThe organic layer was separated
washwashed with brine (100 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-a5ab4595cf5f460c96726c0638ee83e9
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129403B2

Reaction notes

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