Sodium hydride → HCID 131734062, compound

HRID 714557Notes

Reaction equation

[H-].[Na+].[CH:3]12[CH:8]([CH2:9][OH:10])[CH:7]1[CH2:6][O:5][CH2:4]2.[Cl:11][C:12]1[CH:13]=[C:14]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:15]=[CH:16][C:17]=1[F:18]>CN(C=O)C>[CH:3]12[CH:8]([CH2:9][O:10][C:22]3[N:21]=[C:20]([NH:19][C:14]4[CH:15]=[CH:16][C:17]([F:18])=[C:12]([Cl:11])[CH:13]=4)[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=4)[N:23]=3)[CH:7]1[CH2:6][O:5][CH2:4]2

Participants

Conditions

Temperature: 0 °C

Procedure

NaH (60% dispersion in mineral oil, 480 mg, 12.0 mmol) was added in portions to a stirring solution of (3-oxa-bicyclo[3.1.0]hexan-6-yl)methanol (570 mg, 5.0 mmol; prepared according to procedures described in WO2012/021591A1) in DMF (40 mL) at room temperature under N2 (g) atmosphere. After 20 min, the mixture was cooled to 0° C., followed by addition N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine 1a (1.54 g, 4.6 mmol, prepared according to Smaill, J. B., et al., Journal of Medicinal Chemistry, 2000, 43, 1380-1397). The reaction was quenched after stirring 30 min at 0° C. by a slow addition of saturated NH4Cl, followed by extraction with EtOAc (100 mL). The organic layer was washed with H2O (2×50 mL), brine (50 mL), dried over MgSO4, and concentrated to a yellow residue 2b, product was used directly for the next step. MS m/z (ESI+), 431 [M+1].

Workup

customThe reaction was quenched
extractionfollowed by extraction with EtOAc (100 mL)
washThe organic layer was washed with H2O (2×50 mL), brine (50 mL)
dry with materialdried over MgSO4
concentrationconcentrated to a yellow residue 2b, product

Sources & evidence

ORD record: ord-a0db2973e44d4ecd8185de16b9b8e862
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187459B2

Reaction notes

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