Cesium carbonate → N-{3-Amino-1-[6-amino-5-(4-fluoro-phenyl)-pyrimidin-4-yl]-pyrrolidin-3-ylmethyl}-2,4-difluoro-benzamide

HRID 632733Notes

Reaction equation

[NH2:1][C:2]1([CH2:15][NH:16][C:17](=[O:26])[C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[F:25])[CH2:6][CH2:5][N:4]([C:7]2[C:12](Br)=[C:11]([NH2:14])[N:10]=[CH:9][N:8]=2)[CH2:3]1.[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1([CH2:15][NH:16][C:17](=[O:26])[C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[F:25])[CH2:6][CH2:5][N:4]([C:7]2[C:12]([C:31]3[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=3)=[C:11]([NH2:14])[N:10]=[CH:9][N:8]=2)[CH2:3]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of N-{[3-amino-1-(6-amino-5-bromopyrimidin-4-yl)pyrrolidin-3-yl]methyl}-2,4-difluorobenzamide (70.0 mg; 0.16 mmol; 1.0 eq.), 4-fluorophenylboronic acid (45.8 mg; 0.33 mmol; 2.0 eq.), palladium acetate (1.8 mg; 0.01 mmol; 0.05 eq.), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (6.7 mg; 0.02 mmol; 0.10 eq.) and cesium carbonate (160.1 mg; 0.49 mmol; 3.0 eq.) in dioxane (4 ml) and water (0.5 ml) in the microwave vial was heated at 100° C. for 30 min. The reaction mixture was workup and the crude was purified by pre-HPLC (Waters, acetonitrile/0.1% NH4OH in water) to afford the title compound in 61% yield. LC-MS: (M+1=443, obsd.=443).

Workup

customthe crude was purified by pre-HPLC (Waters, acetonitrile/0.1% NH4OH in water)

Sources & evidence

ORD record: ord-6b63bfc9ecd14727bfdc4d3e1279b66e
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321760B2

Reaction notes

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