Triethylamine → N-benzyl-N-{[4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclohexyl]methyl}-N'-(3,5-dimethylbenzoyl)sulfamide

HRID 23749

反応式

HRID 23749 の反応式
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=1)[C:5]([OH:7])=O.ClS(N=C=O)(=O)=O.[CH2:19]([N:26]([CH2:31][CH:32]1[CH2:37][CH2:36][CH:35]([CH2:38][O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41])[CH2:34][CH2:33]1)[S:27]([NH2:30])(=[O:29])=[O:28])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(CC)CC)C>ClCCl>[CH2:19]([N:26]([CH2:31][CH:32]1[CH2:37][CH2:36][CH:35]([CH2:38][O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:41])[CH3:42])[CH2:34][CH2:33]1)[S:27]([NH:30][C:5](=[O:7])[C:4]1[CH:8]=[C:9]([CH3:11])[CH:10]=[C:2]([CH3:1])[CH:3]=1)(=[O:28])=[O:29])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 103563,5-Dimethylbenzoic acidHCID 70918Chlorosulfonyl isocyanateHCID 22574471N-benzyl-N-{[4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclohexyl]methyl}sulfamide

生成物 1

HCID 20757669N-benzyl-N-{[4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclohexyl]methyl}-N'-(3,5-dimethylbenzoyl)sulfamide収率 86%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

3,5-Dimethylbenzoic acid (1.50 g, 10.0 mmole, 1.0 eq) was suspended in 5 mL dichloromethane and heated to reflux, after which a solution of chlorosulfonyl isocyanate (0.87 mL, 10.0 mmole, 1.0 eq) in 2 mL dichloromethane was added. Reaction mixture became clear, and remained so after 40 minutes of reflux. Cooled to room temperature, added hexanes and began to evaporate when solid precipitated out. Recovered filtered solid. 23 mg, 92 μmole, 1.0 eq of this material was added to a mixture of intermediate (2) (34 mg, 92 μmole, 1.0 eq) and triethylamine (39 μL, 277 μmole, 3.0 eq) in dichloromethane (0.5 mL). Reaction was complete at 2 hours, at which point it was purified directly by silica gel chromatography to give the title compound in 86% yield. 1H NMR (500 MHz, DMSO-d6): δ 11.84 (s, 1H), 7.49 (s, 2H), 7.31 (m, 6H), 4.52 (s, 2H), 3.28 (d, 2H), 3.09 (d, 2H), 2.30 (s, 6H), 1.58 (m, 4H), 1.31 (m, 1H), 1.22 (m, 1H), 0.82 (s, 9H), 0.66 (m, 4H), 0.04 (s, 6H). N-benzyl-N′-(3,5-dimethylbenzoyl)-N-{[4-(hydroxymethyl)cyclohexyl]methyl}sulfamide (38): Intermediate (37) was treated as (3) was treated in the synthesis of (4) to give the title alcohol in quantitative yield. 1H NMR (500 MHz, DMSO-d6): δ 11.85 (s, 1H), 7.50 (s, 2H), 7.31 (m, 6H), 4.52 (s, 2H), 4.27 (t, 1H), 3.10 (m, 4H), 2.32 (s, 6H), 1.59 (m, 4H), 1.31 (m, 1H), 1.22 (m, 1H), 0.66 (m, 4H). {4-[(benzyl{[(3,5-dimethylbenzoyl)amino]sulfonyl}amino)methyl]cyclohexyl}methyl phenylcarbamate (39): Alcohol (38) (34.6 mg, 78 mmole, 1.0 eq) in 0.5 mL dichloromethane was treated with triethylamine (38 mL, 272 mmole, 3.5 eq) and phenyl isocyanate (17 mL, 156 mmole, 2.0 eq) to give the title compound after preparative TLC. 1H NMR (500 MHz, DMSO-d6): δ 11.85 (s, 1H), 9.52 (s, 1H), 7.50 (s, 2H), 7.41 (d, 2H), 7.36 (d, 2H), 7.30 (t, 2H), 7.24 (t, 3H), 7.19 (s, 1H), 6.95 (t, 1H), 4.48 (s, 2H), 3.800 (d, 2H), 3.07 (d, 2H), 2.32 (s, 6H), 1.64 (m, 4H), 1.47 (m, 1H), 1.34 (m, 1H), 0.73 (m, 4H).

後処理

  1. temperatureheated
  2. temperatureto reflux
  3. customReaction mixture
  4. temperatureof reflux
  5. customto evaporate when solid
  6. customprecipitated out
  7. customRecovered
  8. filtrationfiltered solid
  9. customReaction
  10. waitwas complete at 2 hours, at which point it
  11. customwas purified directly by silica gel chromatography

出典と根拠

ORDレコード
ord-54e8d92af288423ab066c8b7a907c207
出典データセット
uspto-grants-2005_02
特許番号
US06852738B2

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