Ammonium Chloride → (S)-5-Chloro-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,3,6-triamine

HRID 75882Notes

Reaction equation

[Cl:1][C:2]1[C:3]([NH:21][C:22]2[CH:26]=[C:25]([CH:27]3[CH2:29][CH2:28]3)[NH:24][N:23]=2)=[N:4][C:5]([NH:11][C@H:12]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH3:13])=[C:6]([N+:8]([O-])=O)[CH:7]=1.[Cl-].[NH4+].C([O-])(=O)C.[NH4+]>CO.C1COCC1.[Zn]>[Cl:1][C:2]1[CH:7]=[C:6]([NH2:8])[C:5]([NH:11][C@H:12]([C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[CH3:13])=[N:4][C:3]=1[NH:21][C:22]1[CH:26]=[C:25]([CH:27]2[CH2:29][CH2:28]2)[NH:24][N:23]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a suspension of (S)-3-chloro-N2-(5-cyclopropyl-1H-pyrazol-3-yl)-N6-(1-(4-fluorophenyl)ethyl)-5-nitropyridin-2,6-diamine (Example 36; 0.57 g, 1.37 mmol) and zinc dust (0.447 g, 6.84 mmol) in MeOH:THF (1:1, 24 ml) was slowly added saturated ammonium chloride solution (3.5 ml). The reaction mixture was stirred at 25° C. for 2 hours, followed by addition of saturated ammonium acetate solution (5 ml). The resulting mixture was stirred for another 30 minutes. Zn dust was removed by filtration and washed with EtOAc (20 ml). The organic layer was separated, washed with brine (10 ml), dried over Na2SO4 and the solvent removed to give the title compound. MS: Calcd.: 386. Found: [M+H]+ 387.

Workup

stirringThe resulting mixture was stirred for another 30 minutes
customZn dust was removed by filtration
washwashed with EtOAc (20 ml)
customThe organic layer was separated
washwashed with brine (10 ml)
dry with materialdried over Na2SO4
customthe solvent removed

Sources & evidence

ORD record: ord-da413a9235ea48c5b52037706469a8fc
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835465B2

Reaction notes

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