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

HRID 2062197
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HRID 2062197 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:33])[C@H:26]([OH:32])[CH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:21][CH2:20]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:34])=[CH:14][CH:15]=2)[N:10]=1.CCOCC.[ClH:40]>C(Cl)Cl>[ClH:40].[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:33])[C@H:26]([OH:32])[CH2:27][C:28]([CH3:29])([CH3:30])[CH3:31])[CH2:23][CH2:24]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:34])=[CH:14][CH:15]=2)[N:10]=1
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참가 물질

5

반응물 3

HCID 313Hydrochloric Acid2회HCID 3283Diethyl Ether2회HCID 135438360HCID 135438360, 화합물

생성물 1

HCID 136366706(R)-1-(4-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4,4-dimethylpentan-1-one hydrochloride수율 92%

시약·촉매·용매 1

HCID 6344Dichloromethane
용매

실험 절차

(R)-1-(4-(2-(2-Fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4,4-dimethylpentan-1-one (171 mg, 0.367 mmol) was dissolved in anhydrous CH2Cl2 (2 mL) followed by the addition of Et2O (6 ml) under an N2 atmosphere. A 2.0 M HCl solution in Et2O (0.184 mL, 0.367 mmol) was added over a 1 minute period. The reaction solution changed from a clear yellow solution to a milky white slurry. After complete addition of the HCl solution, the reaction was allowed to stir for an additional 10 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-4,4-dimethylpentan-1-one hydrochloride as a light yellow solid (170 mg, 92%). LC/MS: m/z 467.3 (M+H)+ at 2.60 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.17 (d, J=8.3 Hz, 1H), 7.66 (s, 1H), 7.56 (d, J=8.1 Hz, 1H), 7.48-7.43 (m, 1H), 6.92-6.83 (m, 2H), 4.44-4.41 (m, 1H), 3.87-3.68 (m, 8H), 2.56 (s, 3H), 1.55 (dd, J=14.3, 3.0 Hz, 1H), 1.41 (dd, J=14.3, 8.8 Hz, 1H), 0.96 (s, 9H).

후처리

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

출처 및 근거

ORD 기록
ord-b3da265de80340f28cabf5f20bd79033
출처 데이터셋
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08283354B2

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