Dimethylformamide → 4,5-Dihydro-6-oxa-1-thia-3-aza-benzo[e]azulene-2-carboxylic acid (2-chloro-phenyl)-methyl-amide

HRID 84616

反応式

HRID 84616 の反応式
[S:1]1[C:10]2[C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[O:7][CH2:6][CH2:5][C:4]=2[N:3]=[C:2]1[C:15]([OH:17])=O.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[Cl:29][C:30]1[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=1[NH:32][CH3:33]>C(Cl)Cl>[Cl:29][C:30]1[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=1[N:32]([CH3:33])[C:15]([C:2]1[S:1][C:10]2[C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[O:7][CH2:6][CH2:5][C:4]=2[N:3]=1)=[O:17]

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 136736Benzenamine, 2-chloro-N-methyl-HCID 866348484,5-Dihydro-6-oxa-1-thia-3-aza-benzo[e]azulene-2-carboxylic acid

生成物 1

HCID 579004944,5-Dihydro-6-oxa-1-thia-3-aza-benzo[e]azulene-2-carboxylic acid (2-chloro-phenyl)-methyl-amide収率 30%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a suspension of 4,5-dihydro-6-oxa-1-thia-3-aza-benzo[e]azulene-2-carboxylic acid (1 eq, 0.38 mmol, 101 mg) in anhydrous DCM (3 ml), I drop of DMF was added, followed by 2M oxalyl chloride in DCM (1.7 eq, 0.65 mmol, 330 ul) dropwise. Effervescence was seen and the reaction was stirred at room temperature for 40 mins before evaporating in vacuo. The crude material was dissolved in DCM (3 ml) and 2-chloro-N-methyl aniline (2 eq, 0.76 mmol, 94 ul) was added. The reaction was stirred at room temperature for 16 hr and extracted into DCM, washed with aq K2CO3, the organic layer dried over MgSO4, filtered, and purified on silica (ISCO, gradient 0% ethyl acetate/petrol to 25% ethyl acetate/petrol) to give 326 as a white solid (42 mg, yield 30%). 1H NMR DMSO, 2.89-2.92 (2H, m), 3.43 (3H, s), 4.23 (2H, br. m), 7.02 (1H, d, J=8.4), 7.08 (1H, t, J=7.6), 7.26 (1H, t, J=8), 7.38-7.41 (2H, m), 7.48-7.51 (2H, m), 7.58 (1H, d, J=8.4). MS: (ESI+): MH+ 371, purity >95%.

後処理

  1. additionwas added
  2. custombefore evaporating in vacuo
  3. dissolutionThe crude material was dissolved in DCM (3 ml)
  4. stirringThe reaction was stirred at room temperature for 16 hr
  5. extractionextracted into DCM
  6. washwashed with aq K2CO3
  7. dry with materialthe organic layer dried over MgSO4
  8. filtrationfiltered
  9. custompurified on silica (ISCO, gradient 0% ethyl acetate/petrol to 25% ethyl acetate/petrol)

出典と根拠

ORDレコード
ord-fa8cc5932a014b2c9839bd2d5c545949
出典データセット
uspto-grants-2014_09
特許番号
US08846762B2

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