Cesium carbonate → [2-(5-Chloro-2-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-4-yl]-(3-methylpyridin-4-yl)-amine

HRID 1010857Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:19])=[C:6]([C:8]2[N:17]=[C:16](I)[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[N:9]=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.[NH2:66][C:67]1[CH:72]=[CH:71][N:70]=[CH:69][C:68]=1[CH3:73].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:19])=[C:6]([C:8]2[N:17]=[C:16]([NH:66][C:67]3[CH:72]=[CH:71][N:70]=[CH:69][C:68]=3[CH3:73])[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[N:9]=2)[CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

The crude 2-(5-chloro-2-fluorophenyl)-4-iodo-5,6,7,8-tetrahydroquinazoline (130 mg, 0.35 mmol, 1 eq) was dissolved in dioxane (5 ml) and to this was added Pd(OAc)2 (4 mg, 0.02 mmol, 0.05 eq) followed by BINAP (16 mg, 0.03 mmol, 0.075 eq), 4-amino-3-picoline (49 mg, 0.45 mmol, 1.3 eq) and Cs2CO3 (170 mg, 0.52 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 (1:1/ethyl acetate:hexane) to afford [2-(5-chloro-2-fluoro-phenyl)-5,6,7,8-tetrahydroquinazolin-4-yl]-(3-methylpyridin-4-yl)-amine, compound of formula (38) (110 mg, 86%).

Workup

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

Sources & evidence

ORD record: ord-2ffdd6092b164300a3d431fef0488849
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977342B2

Reaction notes

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