Water → HCID 58710713, compound

HRID 1442995Notes

Reaction equation

[CH3:1][O:2][CH2:3][CH2:4]Br.C(=O)([O-])[O-].[K+].[K+].[Cl:12][C:13]1[CH:14]=[C:15]([CH:39]=[CH:40][C:41]=1[F:42])[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([OH:38])=[CH:24][C:25]=2[O:27][CH2:28][C@H:29]2[CH2:33][CH2:32][CH2:31][N:30]2[C:34](=[O:37])[CH2:35][OH:36])[N:20]=[CH:19][N:18]=1.O>CN(C=O)C>[Cl:12][C:13]1[CH:14]=[C:15]([CH:39]=[CH:40][C:41]=1[F:42])[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:38][CH2:4][CH2:3][O:2][CH3:1])=[CH:24][C:25]=2[O:27][CH2:28][C@H:29]2[CH2:33][CH2:32][CH2:31][N:30]2[C:34](=[O:37])[CH2:35][OH:36])[N:20]=[CH:19][N:18]=1

Participants

Conditions

Temperature: 40 °C

Procedure

2-Bromoethyl methyl ether (22 μl) and potassium carbonate (43 mg) were added to a mixture of 4-[3-chloro-4-fluoroanilino]-5-{[(2R)-1-glycoloylpyrrolidin-2-yl]-methoxy}-quinazolin-7-ol (70 mg) in DMF and the reaction mixture was heated at 40° C. for 16 hours. The reaction mixture was cooled to room temperature and then water (5 ml) was added to leave a white precipitate. The precipitate was filtered, washed with water and then purified by column chromatography using 2-5% methanol in DCM as eluent to give the title compound as a white solid (51 mg, 64%); NMR Spectrum (DMSO-d6 at 373 K) 9.80 (br s, 1H), 8.40 (s, 1H), 8.15 (m, 1H), 7.65 (m, 1H), 7.33 (m, 1H), 6.80 (m, 2H), 4.60 (m, 1H), 4.50 (m, 1H), 4.30-4.10 (m, 4H), 4.0 (m, 2H), 3.75 (t, 2H), 3.50-3.37 (m, 2H), 3.35 (s, 3H), 2.10-1.85 (m, 4H); Mass spectrum MH+ 505.

Workup

temperatureThe reaction mixture was cooled to room temperature
customto leave a white precipitate
filtrationThe precipitate was filtered
washwashed with water
custompurified by column chromatography

Sources & evidence

ORD record: ord-c197342e049f44a8bc05d430835601b4
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07659279B2

Reaction notes

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