Cesium carbonate → [2-(5-Chloro-2-fluorophenyl)-5-methyl-6,7-dihydro-5H-cyclopentapyrimidin-4-yl]-(3-methyl-pyridin-4-yl)-amine

HRID 1354336Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 2-(5-chloro-2-fluorophenyl)-4-iodo-5-methyl-6,7-dihydro-5H-cyclopentapyrimidine (275 mg, 0.71 mmol, 1 eq) in dioxane (5 ml) was added Pd(OAc)2 (8 mg, 0.04 mmol, 0.05 eq) followed by BINAP (33 mg, 0.05 mmol, 0.075 eq), 4-amino-3-picoline (84 mg, 0.78 mmol, 1.1 eq) and Cs2CO3 (347 mg, 1.06 mmol, 1.5 eq). The reaction mixture was heated to 80° C. for 15 h. The reaction mixture was cooled to rt and filtered through Celite® and the crude material was purified by flash column chromatography (1:1/ethyl acetate:hexane-100% ethyl acetate) to afford [2-(5-chloro-2-fluorophenyl)-5-methyl-6,7-dihydro-5H-cyclopentapyrimidin-4-yl]-(3-methyl-pyridin-4-yl)-amine, 43 (250 mg, 96%).

Workup

temperatureThe reaction mixture was cooled to rt
filtrationfiltered through Celite®
customthe crude material was purified by flash column chromatography (1:1/ethyl acetate:hexane-100% ethyl acetate)

Sources & evidence

ORD record: ord-6d62f7458ac442a6a83a97fbf7c6158a
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07223766B2

Reaction notes

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