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Dimethylformamide → neopentyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate

HRID 2079437
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HRID 2079437 반응식
[NH2:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=3)[N:11]=[C:10]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[OH:25])[N:9]=2)[CH2:4]1.CN(C=O)C.C(N(CC)CC)C.Cl[C:39]([O:41][CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:40]>C(Cl)Cl>[OH:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[C:10]1[N:9]=[C:8]([N:5]2[CH2:6][CH2:7][C@@H:3]([CH2:2][NH:1][C:39](=[O:40])[O:41][CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:4]2)[C:17]2[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=2)[N:11]=1
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반응물 4

HCID 6228Dimethylformamide2회HCID 8471TriethylamineHCID 33521852,2-Dimethylpropyl carbonochloridateHCID 1361213492-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol

생성물 1

HCID 136121466neopentyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate수율 94%

시약·촉매·용매

1
HCID 6344Dichloromethane용매

실험 절차

A mixture of 2-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol (200 mg, 0.6 mmol), DMF (6.0 mL), and DMF (1 mL) was stirred under an N2 atmosphere. Triethylamine (0.166 mL, 1.2 mmol) was added, and the reaction was cooled in an ice bath. To this was added 1 M neopentyl chloroformate solution (89 μL in 600 μL THF, 0.6 mmol). After allowing the reaction mixture to warm to room temperature over a period of 30 minutes, CH2Cl2 was added to the reaction mixture, and it was washed once with water before it was dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 0-20% EtOAc in CH2Cl2/hexanes (1:1) gave neopentyl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate (222 mg, 94%). LC/MS: m/z 449 (M+H)+ at 2.73 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, acetic acid-d4) δ 8.42 (dd, J=8.1, 1.8 Hz, 1H), 8.20 (d, J=8.7 Hz, 1H), 7.57 (s, 1H), 7.40-7.29 (m, 3H), 6.92-6.89 (m, 2H), 4.11-3.92 (m, 3H), 3.78-3.61 (m, 3H), 3.33-3.28 (m, 1H), 3.23-3.10 (m, 2H), 2.49 (s, 3H), 2.16-2.08 (m, 1H), 1.83-1.75 (m, 1H), 0.89 (s, 9H) ppm.

후처리

  1. temperaturethe reaction was cooled in an ice bath
  2. washwas washed once with water before it
  3. dry with materialwas dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via silica gel chromatography

출처 및 근거

ORD 기록
ord-1bb9359348c44fda8557ae775a0b1c2b
출처 데이터셋
uspto-grants-2011_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07928107B2

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