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Dimethyl Sulfoxide → 4-(6-Methoxy-7-morpholin-4-yl-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1170254
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HRID 1170254 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[C:21](F)[CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CS(C)=O.[O:35]([CH3:37])[K].CO.[Al]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[C:21]([O:35][CH3:37])[CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 4

HCID 679Dimethyl SulfoxideHCID 5359268AluminumHCID 595517374-(6-Fluoro-7-morpholin-4-yl-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl esterHCID 178501898HCID 178501898, 화합물

생성물 1

HCID 595517184-(6-Methoxy-7-morpholin-4-yl-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester수율 67.2%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

A mixture of 4-(6-Fluoro-7-morpholin-4-yl-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (28.9 mg, 69.5 μmol), as prepared in Example 94a, DMSO (50 μL), and 10M KOMe/MeOH (140 μL, 140 μmol) was stirred in a sealed vial at 100° C. (aluminum block) for 13 hr. The crude reaction was then diluted with toluene and directly loaded onto a silica flash column (1:2 hexanes/EtOAc eluent) to provide the title compound (20.0 mg, 67%). NOe experiments support the assigned regioisomer. Select 1H-NMR resonances and nOes (300 MHz, CDCl3) δ 7.36 (s, 1H), 7.25 (s, 1H), 4.05 (s, 3H), 3.51 (m, 1H). Irradiation of the diagnostic methine proton at δ 3.51 generates an nOe to the quinazoline C5 proton at δ 7.25, but not to the quinazoline C8 proton at δ 7.36. Irradiation of the methoxy protons at δ 4.05 generates an nOe to the C5 proton at δ 7.25, but not to the C8 proton at δ 7.36. This indicates methoxy substitution at C6 of the quinazoline. LC/MS (ESI): calcd mass 428.2, found 429.3 (MH)+.

후처리

  1. customThe crude reaction

출처 및 근거

ORD 기록
ord-3d21726e0c2d42c088fa80efd01c38d3
출처 데이터셋
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07825244B2

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