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Acetic Acid → (+/-)-2-[4-(4-Amino-quinazolin-7-ylmethyl)-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl]-5-chloro-indole-1-carboxylic acid tert-butyl ester

HRID 1433012
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HRID 1433012 반응식
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH2:18][N:19]1[CH2:24][C:23](=[O:25])[N:22]([CH2:26][C:27]2[CH:32]=C[C:30](C#N)=[C:29](N)[CH:28]=2)[CH:21]([C:36]([O:38][CH3:39])=[O:37])[CH2:20]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:40]1[CH:45]=[N:44][CH:43]=[N:42][CH:41]=1.CC(O)=O>CCO>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[CH2:18][N:19]1[CH2:24][C:23](=[O:25])[N:22]([CH2:26][C:27]2[CH:32]=[C:41]3[C:30]([C:45]([NH2:40])=[N:44][CH:43]=[N:42]3)=[CH:29][CH:28]=2)[CH:21]([C:36]([O:38][CH3:39])=[O:37])[CH2:20]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 176Acetic Acid2회HCID 92621,3,5-Triazine2회HCID 54288444(+/-)-2-[4-(3-Amino-4-cyano-benzyl)-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl]-5-chloro-indole-1-carboxylic acid tert-butyl ester

생성물 1

HCID 53785442(+/-)-2-[4-(4-Amino-quinazolin-7-ylmethyl)-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl]-5-chloro-indole-1-carboxylic acid tert-butyl ester수율 24.9%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

A solution containing (±)-2-[4-(3-amino-4-cyano-benzyl)-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl]-5-chloro-indole-1-carboxylic acid tert-butyl ester (100 mg, 0.18 mmol), 1,3,5-triazine (146 mg, 1.81 mmol), and glacial HOAc (99 mg, 1.81 mmol) in absolute EtOH (10 mL) is maintained at reflux for 16 hours. A second portion of 1,3,5-triazine (146 mg, 1.81 mmol) and glacial HOAc (99 mg, 1.81 mmol) is added and the reaction mixture is maintained at reflux for an additional 16 hours. The reaction mixture is concentrated in vacuo and the crude product is diluted with water/CH3CN and purified by reverse-phase HPLC [Buffer A: water w/0.1% TFA; Buffer B: CH3CN w/0.1% TFA; Gradient: 0% B to 60% B over 30 min] to provide 26 mg (20%) of the title compound as a white solid which is used directly in the next reaction without further characterization.

후처리

  1. temperatureis maintained
  2. temperatureat reflux for 16 hours
  3. temperaturethe reaction mixture is maintained
  4. temperatureat reflux for an additional 16 hours
  5. concentrationThe reaction mixture is concentrated in vacuo
  6. additionthe crude product is diluted with water/CH3CN
  7. custompurified by reverse-phase HPLC [Buffer A: water

출처 및 근거

ORD 기록
ord-cee5dbd33fd143108fdaeb94cacefb81
출처 데이터셋
uspto-grants-2009_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07612075B2

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