Hydrochloric Acid → (R)-1-(4-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one hydrochloride

HRID 2079309노트

반응식

HRID 2079309 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[C:9]1[N:18]=[C:17]([N:19]2[CH2:24][CH2:23][N:22]([C:25](=[O:32])[C@H:26]([OH:31])[CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:21][CH2:20]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:33])=[CH:14][CH:15]=2)[N:10]=1.CCOCC.[ClH:39]>C(Cl)Cl>[ClH:39].[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[C:9]1[N:18]=[C:17]([N:19]2[CH2:20][CH2:21][N:22]([C:25](=[O:32])[C@H:26]([OH:31])[CH2:27][CH:28]([CH3:29])[CH3:30])[CH2:23][CH2:24]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:33])=[CH:14][CH:15]=2)[N:10]=1

참가 물질

5

반응물 3

HCID 313Hydrochloric Acid2회HCID 3283Diethyl Ether2회HCID 135453120(R)-1-(4-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one

생성물 1

HCID 136366945(R)-1-(4-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one hydrochloride수율 92%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

(R)-1-(4-(2-(2-Fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one (406 mg, 0.898 mmol) was dissolved in anhydrous CH2Cl2 (3 mL) followed by the addition of Et2O (6 mL) under an N2 atmosphere. A 2.0 M HCl solution in Et2O (0.449 mL, 0.898 mmol) was added over a 2-minute period. The reaction solution changed from a clear yellow solution to a turbid white slurry. After complete addition of the HCl solution, the reaction was allowed to stir for an additional 15 minutes. The product was collected by vacuum filtration and dried under vacuum to obtain (R)-1-(4-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one hydrochloride as a white solid (403 mg, 92%). LC/MS: m/z 453.5 (M+H)+ at 2.44 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) d 8.20 (d, J=8.7 Hz, 1H), 7.71 (s, 1H), 7.60-7.60 (m, 1H), 7.50-7.44 (m, 1H), 6.99 (d, J=8.4 Hz, 1H), 6.87 (t, J=9.1 Hz, 1H), 4.36-4.33 (m, 1H), 4.25-3.67 (m, 8H), 2.57 (s, 3H), 1.83-1.71 (m, 1H), 1.49-1.35 (m, 2H), 0.91 (d, J=6.7 Hz, 6H) ppm.

후처리

  1. filtrationThe product was collected by vacuum filtration
  2. customdried under vacuum

출처 및 근거

ORD 기록
ord-b726b57895ff43a5bf1c14eb0cc583ab
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07928107B2

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