Methanol → 2-(2,6-Dimethylpyridin-4-yl)-7-methoxy-5-(2-(pyrrolidin-1-yl)ethoxy)quinazolin-4(3H)-one

HRID 591811Notes

Reaction equation

[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12](F)=[CH:13][C:14]=3[O:19][CH2:20][CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[N:9]=2)[CH:5]=[C:4]([CH3:28])[N:3]=1.[CH3:29][O-:30].[Na+].CO.O>CN(C=O)C.C(O)(=O)C>[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12]([O:30][CH3:29])=[CH:13][C:14]=3[O:19][CH2:20][CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[N:9]=2)[CH:5]=[C:4]([CH3:28])[N:3]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 2-(2,6-dimethyl-pyridin-4-yl)-7-fluoro-5-(2-pyrrolidin-1-yl-ethoxy)-3H-quinazolin-4-one (0.30 g, 0.80 mmol) in anhydrous DMF (5 mL) was added a solution of sodium methoxide in methanol (25 wt %, 0.43 g, 8.00 mmol) and the reaction mixture was stirred at 70° C. for 16 h. After cooling to room temperature, water (10 mL) was added, and the mixture was neutralized to pH approximately 6 with acetic acid. The solvent was evaporated, and the residue was purified by the Simpliflash system (2% methanol in CH2Cl2 and then 4% 7.0 M ammonia in methanol and CH2Cl2 as eluent) to give the title compound as a yellow solid. Yield: 0.100 g (32%). MP 190-191° C. 1H NMR (400 MHz, CDCl3): δ 7.59 (s, 2H), 6.86 (d, J=1.95 Hz, 1H), 6.53 (d, J=1.95 Hz, 1H), 4.25 (t, J=6.05 Hz, 2H), 3.93 (s, 3H), 3.03 (t, J=6.24 Hz, 2H), 2.69 (br s, 4H), 2.64 (s, 6H), 1.93-1.70 (m, 4H). MS (ES+) m/z: 395.22 (M+1) and 298.12 (100%).

Workup

temperatureAfter cooling to room temperature
customThe solvent was evaporated
customthe residue was purified by the Simpliflash system (2% methanol in CH2Cl2

Sources & evidence

ORD record: ord-a4a7a2ebfc034f4391d962159536d573
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238640B2

Reaction notes

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