Potassium Carbonate → (R)-benzyl-1-((5-cyano-6-(3-(pyrimidin-2-yl)phenylamino)pyrazin-2-ylamino)(cyclopropyl)methyl)cyclopropylcarbamate

HRID 332818Notes

Reaction equation

[CH2:1]([O:8][C:9](=[O:28])[NH:10][C:11]1([C@H:14]([NH:18][C:19]2[CH:24]=[N:23][C:22]([C:25]#[N:26])=[C:21](Cl)[N:20]=2)[CH:15]2[CH2:17][CH2:16]2)[CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:29]1[CH:34]=[CH:33][CH:32]=[N:31][C:30]=1[C:35]1[CH:36]=[C:37]([CH:39]=[CH:40][CH:41]=1)[NH2:38].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.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:8][C:9](=[O:28])[NH:10][C:11]1([C@H:14]([NH:18][C:19]2[CH:24]=[N:23][C:22]([C:25]#[N:26])=[C:21]([NH:38][C:37]3[CH:39]=[CH:40][CH:41]=[C:35]([C:30]4[N:29]=[CH:34][CH:33]=[CH:32][N:31]=4)[CH:36]=3)[N:20]=2)[CH:15]2[CH2:17][CH2:16]2)[CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a mixture of (R)-benzyl-1-((6-chloro-5-cyanopyrazin-2-ylamino)(cyclopropyl)methyl)cyclopropylcarbamate (80 mg, 0.20 mmol) in Dioxane (2 mL) was added 3-(pyrimidin-2-yl)aniline (41 mg, 0.24 mmol), Pd(OAc)2 (9 mg, 0.04 mmol), BINAP (25 mg, 0.04 mmol) and K2CO3 (83 mg, 0.6 mmol). After heating at 95° C. for 2 h, the mixture was filtered, the filtrate was concentrated and purified by preparative HPLC to give (R)-benzyl-1-((5-cyano-6-(3-(pyrimidin-2-yl)phenylamino)pyrazin-2-ylamino)(cyclopropyl)methyl)cyclopropylcarbamate.

Workup

filtrationthe mixture was filtered
concentrationthe filtrate was concentrated
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-cb619ffa06484dca83062f268852e66e
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877760B2

Reaction notes

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