1H-Indole-2-carboxylic acid, 1-methyl- → HCID 178488203, 화합물

HRID 432277

반응식

HRID 432277 반응식
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]([OH:13])=O.C(Cl)(=O)C(Cl)=O.[NH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:35]3[C:30](=[N:31][CH:32]=[N:33][C:34]=3[NH2:36])[N:29]([C@H:37]3[CH2:42][CH2:41][C@H:40]([N:43]4[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]4)[CH2:39][CH2:38]3)[N:28]=2)=[CH:23][C:22]=1[O:50][CH3:51]>ClCCl.CN(C=O)C.N1C=CC=CC=1>[NH2:36][C:34]1[N:33]=[CH:32][N:31]=[C:30]2[N:29]([C@H:37]3[CH2:42][CH2:41][C@H:40]([N:43]4[CH2:44][CH2:45][N:46]([CH3:49])[CH2:47][CH2:48]4)[CH2:39][CH2:38]3)[N:28]=[C:27]([C:24]3[CH:25]=[CH:26][C:21]([NH:20][C:11]([C:3]4[N:2]([CH3:1])[C:10]5[C:5]([CH:4]=4)=[CH:6][CH:7]=[CH:8][CH:9]=5)=[O:13])=[C:22]([O:50][CH3:51])[CH:23]=3)[C:35]=12

참가 물질

7

반응물 3

HCID 276951H-Indole-2-carboxylic acid, 1-methyl-HCID 65578Oxalyl chlorideHCID 178488198HCID 178488198, 화합물

생성물 1

HCID 178488203HCID 178488203, 화합물수율 80.2%

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 1049Pyridine용매HCID 6344Dichloromethane용매2회

실험 절차

To 1-methyl-1H-2-indolecarboxylic acid (0.802 g, 4.58 mmol) in dichloromethane (14 mL) was added oxalyl chloride (4 mL, 45.8 mmol) and DMF (1 drop). The reaction mixture was stirred overnight. Solvent was evaporated and the residue was dissolved in Dichloromethane (5 mL). Half of the dichloromethane solution (2.5 mL) was added to a solution of trans-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.50 g, 1.145 mmol) in pyridine (6 mL) at 0° C. After 30 minutes, the solid was collected by filtration. Water was then added to the solid and the pH of the solution was adjusted to 10 with sodium hydroxide (1.0N). The aqueous was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (80:20) as mobile phase to give trans-N2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide (0.545 g, 80%). 1H NMR (DMSO-d6) δ 1.49 (m, 2H), 2.02 (m, 6H), 2.17 (s, 3H), 2.36 (m, 5H), 2.55 (m, 4H), 3.96 (s, 3H), 4.04 (s, 3H), 4.66 (m, 1H), 7.15 (m, 1H), 7.28-7.35 (m, 4H), 7.58 (d, J=8.42 Hz, 1H), 7.70 (d, J=7.96 Hz, 1H), 8.11 (d, J=8.14, 1H), 8.24 (s, 1H), 9.43 (s, 1H).

후처리

  1. customSolvent was evaporated
  2. dissolutionthe residue was dissolved in Dichloromethane (5 mL)
  3. waitAfter 30 minutes
  4. filtrationthe solid was collected by filtration
  5. additionWater was then added to the solid
  6. extractionThe aqueous was extracted with dichloromethane
  7. washThe combined organic layer was washed with water
  8. dry with materialbrine, dried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by flash column chromatography

출처 및 근거

ORD 기록
ord-61e19df7660c4b549754b01e96efbc6e
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06660744B1

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