Cesium carbonate → 4-[2-(5-Chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidin-4-ylamino]-nicotinic acid ethyl ester

HRID 1354331Notes

Reaction equation

Cl[C:2]1[C:3]2[O:18][CH2:17][CH2:16][C:4]=2[N:5]=[C:6]([C:8]2[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=2[F:15])[N:7]=1.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.[CH2:65]([O:67][C:68](=[O:76])[C:69]1[C:74]([NH2:75])=[CH:73][CH:72]=[N:71][CH:70]=1)[CH3:66].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:65]([O:67][C:68](=[O:76])[C:69]1[C:74]([NH:75][C:2]2[C:3]3[O:18][CH2:17][CH2:16][C:4]=3[N:5]=[C:6]([C:8]3[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=3[F:15])[N:7]=2)=[CH:73][CH:72]=[N:71][CH:70]=1)[CH3:66]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-chloro-2-(5-chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidine (320 mg, 1.13 mmol, 1 eq) in dioxane (5 ml) was added Pd(OAc)2 (13 mg, 0.06 mmol, 0.05 eq) followed by BINAP (53 mg, 0.08 mmol, 0.075 eq), 4-aminonicotinic acid ethyl ester (206 mg, 1.24 mmol, 1.1 eq) and Cs2CO3 (478 mg, 1.46 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 (0-5%MeOH in CHCl3) to afford 4-[2-(5-chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidin-4-ylamino]-nicotinic acid ethyl ester (100 mg, 21%) as a white solid.

Workup

temperatureThe reaction mixture was cooled to rt
filtrationfiltered through Celite®
customthe crude material was purified by flash column chromatography (0-5%MeOH in CHCl3)

Sources & evidence

ORD record: ord-a10040f6302340e595981ccc364794dc
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07223766B2

Reaction notes

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