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

HRID 84616

반응식

HRID 84616 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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%.

후처리

  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)

출처 및 근거

ORD 기록
ord-fa8cc5932a014b2c9839bd2d5c545949
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846762B2

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