Boron tribromide → 4-(methyl(2-methylquinazolin-4-yl)amino)phenol

HRID 1436282Notes

Reaction equation

Cl.C[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]([C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=[C:14]([CH3:22])[N:13]=2)[CH3:11])=[CH:6][CH:5]=1.B(Br)(Br)Br>ClCCl>[OH:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]([C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=[C:14]([CH3:22])[N:13]=2)[CH3:11])=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 10 °C

Procedure

To a solution of (4-methoxy-phenyl)-(2-methyl-quinazolin-4-yl)-methyl-amine hydrochloride salt (106 mg, 0.336 mmol) in dichloromethane (10 mL) at −78° C. was added slowly boron tribromide (1M in CH2Cl2, 0.75 mL) under argon. The cold bath was removed and the reaction mixture was allowed to warm up slowly to 10° C. in 1.5 h. The reaction mixture was quenched with water (10 mL), basified with 2N NaOH to pH=10, and extracted with EtOAc (2×25 mL). The EtOAc extracts were dried and evaporated to give a light brown residue. The crude was purified by column chromatography (SiO2, EtOAc:hexanes/15-50%) to give the product as a white solid, which was further purified by recrystallization from MeOH: 1H NMR (acetone-d6) 8.74 (s, 1H), 7.75 (m, 1H), 7.67 (m, 1H), 7.20-7.18 (m, 3H), 7.12 (m, 1H), 7.04-6.99 (m, 2H), 3.64 (s, 3H), 2.79 (s, 3H).

Workup

customThe cold bath was removed
customThe reaction mixture was quenched with water (10 mL)
extractionextracted with EtOAc (2×25 mL)
dry with materialThe EtOAc extracts were dried
customevaporated
customto give a light brown residue
customThe crude was purified by column chromatography (SiO2, EtOAc:hexanes/15-50%)

Sources & evidence

ORD record: ord-a5a9143b520744bdbcc0867d91edde7d
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618975B2

Reaction notes

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