Cesium carbonate → [2-(5-Chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidin-4-yl]-(3-methyl-pyridin-4-yl)-amine

HRID 1010863Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 2-(5-chloro-2-fluorophenyl)-4-iodo-6,7-dihydrofuro[3,2-d]pyrimidine (106 mg, 0.28 mmol, 1 eq) in dioxane (5 ml) was added Pd(OAc)2 (3 mg, 0.01 mmol, 0.05 eq) followed by BINAP (13 mg, 0.02 mmol, 0.075 eq), 4-amino-3-picoline (40 mg, 0.37 mmol, 1.3 eq) and Cs2CO3 (138 mg, 0.42 mmol, 1.5 eq). The reaction mixture was heated to 80° C. for 15 h. The reaction mixture was cooled to r.t. and filtered through Celite® and the crude material was purified by flash column chromatography (4:1/ethyl acetate:hexane-100% ethylacetate) to afford [2-(5-chloro-2-fluorophenyl)-6,7-dihydrofuro[3,2-d]pyrimidin-4-yl]-(3-methyl-pyridin-4-yl)-amine, i.e. compound of formula (39) (30 mg, 30%) as a white solid.

Workup

temperatureThe reaction mixture was cooled to r.t.
filtrationfiltered through Celite®
customthe crude material was purified by flash column chromatography (4:1/ethyl acetate:hexane-100% ethylacetate)

Sources & evidence

ORD record: ord-153a01ba622b4c7da47faa7837d05c23
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977342B2

Reaction notes

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