Dimethyl Sulfoxide → 6-[(4-tert-Butylphenyl)sulfonyl]-7-methyl-8-(methylsulfonyl)-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine

HRID 1691466

反応式

HRID 1691466 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:6]=2[C:33]=1[CH3:34].[CH3:35][S:36]([O-:38])=[O:37].[Na+].CNCCNC.CS(C)=O>CCOC(C)=O>[C:29]([C:26]1[CH:25]=[CH:24][C:23]([S:20]([N:7]2[C:6]3[C:33]([CH3:34])=[C:2]([S:36]([CH3:35])(=[O:38])=[O:37])[CH:3]=[CH:4][C:5]=3[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:17])([F:18])[F:19])[CH:14]=[CH:15][C:9]=3[CH2:8]2)(=[O:21])=[O:22])=[CH:28][CH:27]=1)([CH3:32])([CH3:30])[CH3:31]

参加物

6

反応物 4

HCID 679Dimethyl SulfoxideHCID 8070N,N'-DimethylethylenediamineHCID 2733271Sodium methanesulfinateHCID 669017308-Bromo-6-[(4-tert-butylphenyl)sulfonyl]-7-methyl-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine2 回

生成物 1

HCID 669016326-[(4-tert-Butylphenyl)sulfonyl]-7-methyl-8-(methylsulfonyl)-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
110 °C

実験手順

A mixture of 8-bromo-6-[(4-tert-butylphenyl)sulfonyl]-7-methyl-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (intermediate 63, 100 mg, 0.180 mmol) sodium methyl sulfinate (55.2 mg, 0.541 mmol) and copper (II) triflate benzene complex (27.2 mg, 0.054 mmol) was flushed with nitrogen and capped, and was added N,N′-dimethyl ethylenediamine (0.12 mL, 0.108 mmol), and DMSO (0.60 mL). The mixture was heated to 110° C. for 36 h. After cooling to rt, the reaction mixture was diluted with EtOAc, filtered through silica gel, the filtrated was washed with water and brine, and concentrated. The residue was purified by reverse phase HPLC to provide the title compound as a racemic mixture. LC/MS: m/e 553.9 (M+H)+; 1H NMR (500 MHz, CD3OD): δ 7.87 (1H, d), 7.63 (1H, d), 7.19 (2H, d), 7.13 (1H, d), 7.07 (1H, d), 7.02 (2H, d), 5.21 (1H, d), 4.45 (1H, d), 3.15 (3H, s), 2.87 (3H, s), 1.23 (9H, s). The racemic mixture was separated on a Chiracel OD-H column eluting with 20% EtOH in hexanes, at 8.0 mL/min. The faster eluting enantiomer E1 has a retention time of 15.7 min. The slower eluting enantiomer E2 has a retention time of 28.5 min.

後処理

  1. customwas flushed with nitrogen
  2. customcapped
  3. temperatureAfter cooling to rt
  4. filtrationfiltered through silica gel
  5. washthe filtrated was washed with water and brine
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase HPLC

出典と根拠

ORDレコード
ord-d38d2bc3226e49b290b52868db4a3c56
出典データセット
uspto-grants-2012_04
特許番号
US08153626B2

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