Acetic Acid → 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(3-(pyrimidin-2-yl)phenylamino)pyrazine-2-carboxamide

HRID 2200432Notes

Reaction equation

HRID 2200432 reaction equation
[NH2:1][C@H:2]1[C:7]([F:9])([F:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:10][C:11]1[N:12]=[C:13]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]3[N:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[CH:21]=2)[C:14]([C:17]#[N:18])=[N:15][CH:16]=1.[OH-].[Na+].OO.CC(O)=[O:38]>CCO.CS(C)=O>[NH2:1][C@H:2]1[C:7]([F:9])([F:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:10][C:11]1[N:12]=[C:13]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]3[N:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[CH:21]=2)[C:14]([C:17]([NH2:18])=[O:38])=[N:15][CH:16]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 866855625-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(3-(pyrimidin-2-yl)phenylamino)pyrazine-2-carbonitrile

Product 1

HCID 866855635-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(3-(pyrimidin-2-yl)phenylamino)pyrazine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolvent

Procedure

A mixture of 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-chloropyrazine-2-carbonitrile (76 mg, 0.264 mmol), 3-(pyrimidin-2-yl)aniline (64 mg, 0.375 mmol), K2CO3 (90 mg, 0.652 mmol), BINAP (30 mg, 0.048 mmol) and Pd(OAc)2 (10 mg, 0.044 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 110 C for 3 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(3-(pyrimidin-2-yl)phenylamino)pyrazine-2-carbonitrile (58 mg). The compound 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-(3-(pyrimidin-2-yl)phenylamino)pyrazine-2-carbonitrile (58 mg, 0.131 mmol) was dissolved in EtOH (2 mL) and DMSO (1 mL), aq. 1N NaOH (1.0 mL) and aq. H2O2 (30%, 1.0 mL) were added. The mixture was stirred at room temperature for 90 min. HOAc (0.5 mL) was added. The mixture was then concentrated in vacuo. The residue was purified by HPLC to give the titled compound (43 mg). MS 441.2 (M+H); UV 201.1, 249.3, 301.5 nm; t 0.462 min.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-3f5cbe6ddcf945e48328eccb5f3dbb22
Source dataset
uspto-grants-2016_06
Patent number
US09359308B2

Reaction notes

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