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

HRID 2079437
ノート
印刷プレビュー

反応式

HRID 2079437 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 6228Dimethylformamide2 回HCID 8471TriethylamineHCID 33521852,2-Dimethylpropyl carbonochloridateHCID 1361213492-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol

生成物 1

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

試薬・触媒・溶媒

1
HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-1bb9359348c44fda8557ae775a0b1c2b
出典データセット
uspto-grants-2011_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07928107B2

反応ノート

読み込み中…

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