Cesium carbonate → 4-[2-(5-Chloro-2-fluoro-phenyl)-6,6-dimethyl-6,7-dihydro-5H-cyclopentapyrimidin-4-ylamino]-nicotinic acid methyl ester

HRID 1010843

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C:8]2[N:13]=[C:12](I)[C:11]3[CH2:15][C:16]([CH3:19])([CH3:18])[CH2:17][C:10]=3[N:9]=2)[CH:7]=1.[CH3:21][O:22][C:23](=[O:31])[C:24]1[C:29]([NH2:30])=[CH:28][CH:27]=[N:26][CH:25]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:21][O:22][C:23](=[O:31])[C:24]1[C:29]([NH:30][C:12]2[C:11]3[CH2:15][C:16]([CH3:19])([CH3:18])[CH2:17][C:10]=3[N:9]=[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[F:20])[N:13]=2)=[CH:28][CH:27]=[N:26][CH:25]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of 2-(5-Chloro-2-fluoro-phenyl)-4-iodo-6,6-dimethyl-6,7-dihydro-5H-cyclopentapyrimidine (500 mg, 1.24 mmol), 4-amino-nicotinic acid methyl ester (208 mg, 1.37 mmol), Pd(OAc)2 (14 mg, 62.09 μmol) and Rac-BINAP (60 mg, 93.14 μmol) in dry dioxane (10 mL) was added Cs2CO3 (607 mg, 1.86 mmol). The mixture was heated for 12 h at 85° C., cooled and evaporated. The residue was purified by chromatography (CH2Cl2, 0-10% MeOH) to give the desired product (178 mg, 34% yield).

Workup

temperaturecooled
customevaporated
customThe residue was purified by chromatography (CH2Cl2, 0-10% MeOH)

Sources & evidence

ORD record: ord-040016ec6429455caa5df4c81638b485
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977342B2

Linked notes

Loading…