Potassium Carbonate → 3-(3-(2H-1,2,3-triazol-2-yl)phenylamino)-5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)pyrazine-2-carbonitrile

HRID 2200429Notes

Reaction equation

HRID 2200429 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](Cl)[C:14]([C:17]#[N:18])=[N:15][CH:16]=1.[N:20]1[N:21]([C:25]2[CH:26]=[C:27]([CH:29]=[CH:30][CH:31]=2)[NH2:28])[N:22]=[CH:23][CH:24]=1.C([O-])([O-])=O.[K+].[K+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[N:20]1[N:21]([C:25]2[CH:26]=[C:27]([NH:28][C:13]3[C:14]([C:17]#[N:18])=[N:15][CH:16]=[C:11]([NH:10][C@@H:3]4[CH2:4][CH2:5][CH2:6][C:7]([F:9])([F:8])[C@@H:2]4[NH2:1])[N:12]=3)[CH:29]=[CH:30][CH:31]=2)[N:22]=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 234387563-(2H-1,2,3-Triazol-2-yl)anilineHCID 866855565-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-chloropyrazine-2-carbonitrile

Product 1

HCID 866855603-(3-(2H-1,2,3-triazol-2-yl)phenylamino)-5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)pyrazine-2-carbonitrileYield 37.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)-3-chloropyrazine-2-carbonitrile (76 mg, 0.264 mmol), 3-(2H-1,2,3-triazol-2-yl)aniline (60 mg, 0.375 mmol), K2CO3 (80 mg, 0.579 mmol), BINAP (25 mg, 0.040 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 3-(3-(2H-1,2,3-triazol-2-yl)phenylamino)-5-((1R,2R)-2-amino-3,3-difluorocyclohexylamino)pyrazine-2-carbonitrile (41 mg).

Workup

  1. customwas degassed with Ar
  2. concentrationThe mixture was concentrated in vacuo
  3. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-7d93ea05949f48fa8e8c1136ed79fda6
Source dataset
uspto-grants-2016_06
Patent number
US09359308B2

Reaction notes

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