Acetic Anhydride → 4-Acetyl-3-{[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amino}-8-fluoro-isochromen-1-one

HRID 1920745

反応式

HRID 1920745 の反応式
[CH:1]1([C@H:4]([NH:12][C:13]([CH2:15][C:16]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:17]=2[C:18](O)=[O:19])=[O:14])[C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[CH:6]=2)[CH2:3][CH2:2]1.[C:26](OC(=O)C)(=[O:28])[CH3:27]>>[C:26]([C:15]1[C:16]2[C:17](=[C:21]([F:25])[CH:22]=[CH:23][CH:24]=2)[C:18](=[O:19])[O:14][C:13]=1[NH:12][C@@H:4]([CH:1]1[CH2:2][CH2:3]1)[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[CH:6]=1)(=[O:28])[CH3:27]

参加物

3

反応物 2

HCID 7918Acetic AnhydrideHCID 577334122-({[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-methyl)-6-fluoro-benzoic acid

生成物 1

HCID 577332754-Acetyl-3-{[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amino}-8-fluoro-isochromen-1-one収率 103.5%

実験手順

A mixture of 2-({[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-methyl)-6-fluoro-benzoic acid (12.92 g, 37.41 mmol) and acetic anhydride (100 mL, 1 mol) was stirred at +65° C. for 20 hours and evaporated in vacuo (65° C., 10 mbar, 2 hours) to give the title compound as a thick brown oil, which was used in the next step without purification (14.30 g, yield 103.5%, purity 95% according to 1H NMR). LC-MS (m/z) 370.1 (MH+); tR=1.65. 1H NMR (500 MHz, DMSO-d6): 0.45-0.59 (m, 3H), 0.64 (m, 1H), 1.41 (m, 1H), 2.53 (s, 3H), 4.36 (t (unres. dd), 1H), 7.03 (dd, J=8.3, 10.7 Hz, 1H), 7.12 (dt, J=1.9, 8.5 Hz, 1H), 7.27 (d, J=10.2 Hz, 1H), 7.3 (d, J=7.8 Hz, 1H), 7.42 (q, J=7.8 Hz, 1H), 7.53 (d, 8.5 Hz, 1H), 7.7 (m, 1H), 11.3 (d, J=7.3 Hz, 1H, NH).

後処理

  1. customevaporated in vacuo (65° C., 10 mbar, 2 hours)

出典と根拠

ORDレコード
ord-3c04d92c813a4550a2d339b12e35f69d
出典データセット
uspto-grants-2012_05
特許番号
US08173639B2

関連ノート

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