Triethylamine → N-[4-(5H-Pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide

HRID 1456130노트

반응식

HRID 1456130 반응식
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][N:11]3[CH:19]=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[O:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:31][C:32]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:33]=1[C:34](Cl)=[O:35]>C(Cl)Cl>[CH:21]1[CH:20]=[CH:19][N:11]2[CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:8]([C:6]([C:5]3[CH:22]=[CH:23][C:2]([NH:1][C:34](=[O:35])[C:33]4[CH:37]=[C:38]([F:41])[CH:39]=[CH:40][C:32]=4[CH3:31])=[CH:3][CH:4]=3)=[O:7])[CH2:9][C:10]=12

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 27373835-Fluoro-2-methylbenzoyl chlorideHCID 1082828010,11-dihydro-10(4-aminobenzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine

생성물 1

HCID 10003306N-[4-(5H-Pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide수율 40.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

To a stirred solution of 500 mg of 10,11-dihydro-10-(4-aminobenzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 3 ml of methylene chloride, cooled to 0° C., under argon, is added 346 μl of triethylamine followed by the addition of 340 mg of 2-methyl-5-fluorobenzoyl chloride in 2 ml of methylene chloride. The cooling bath is removed and stirring continued for 18 hours. After cooling to 0° C., an additional 342 mg of 2-methyl-5-fluorobenzoyl chloride in 2 ml of methylene chloride is added. The cooling bath is removed and stirring continued for 18 hours. The volatiles are removed in vacuo to a residue which is dissolved in 50 ml of methylene chloride and washed with 20 ml each of water, 2N citric acid, 1M sodium bicarbonate and brine. The organic layer is dried over Na2SO4 and passed through a pad of hydrous magnesium silicate. The filtrate is evaporated in vacuo to a residue which is crystallized from ethyl acetatehexane to give 295 mg of the desired product as a white solid, m.p. 170°-180° C.

후처리

  1. customThe cooling bath is removed
  2. additionan additional 342 mg of 2-methyl-5-fluorobenzoyl chloride in 2 ml of methylene chloride is added
  3. customThe cooling bath is removed
  4. stirringstirring
  5. waitcontinued for 18 hours
  6. customThe volatiles are removed in vacuo to a residue which
  7. dissolutionis dissolved in 50 ml of methylene chloride
  8. washwashed with 20 ml each of water, 2N citric acid, 1M sodium bicarbonate and brine
  9. dry with materialThe organic layer is dried over Na2SO4
  10. customThe filtrate is evaporated in vacuo to a residue which
  11. customis crystallized from ethyl acetatehexane

출처 및 근거

ORD 기록
ord-e9067a306a7d435281a48e3a97010736
출처 데이터셋
uspto-grants-1998_12
특허 번호
US05843944

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