Oxalyl chloride → HCID 178488207, 화합물

HRID 897565

반응식

HRID 897565 반응식
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([OH:12])=O.C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[C:34]3[C:29](=[N:30][CH:31]=[N:32][C:33]=3[NH2:35])[N:28]([C@H:36]3[CH2:41][CH2:40][C@H:39]([N:42]4[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]4)[CH2:38][CH2:37]3)[N:27]=2)=[CH:22][C:21]=1[O:49][CH3:50]>ClCCl.CN(C=O)C.N1C=CC=CC=1>[NH2:35][C:33]1[N:32]=[CH:31][N:30]=[C:29]2[N:28]([C@H:36]3[CH2:41][CH2:40][C@H:39]([N:42]4[CH2:43][CH2:44][N:45]([CH3:48])[CH2:46][CH2:47]4)[CH2:38][CH2:37]3)[N:27]=[C:26]([C:23]3[CH:24]=[CH:25][C:20]([NH:19][C:10]([C:2]4[NH:1][C:9]5[C:4]([CH:3]=4)=[CH:5][CH:6]=[CH:7][CH:8]=5)=[O:12])=[C:21]([O:49][CH3:50])[CH:22]=3)[C:34]=12

참가 물질

7

반응물 3

HCID 65578Oxalyl chlorideHCID 72899Indole-2-carboxylic acidHCID 178488198HCID 178488198, 화합물

생성물 1

HCID 178488207HCID 178488207, 화합물수율 47%

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 1049Pyridine용매HCID 6344Dichloromethane용매2회

실험 절차

To 1H-2-indolecarboxylic acid (0.738 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 as 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)-1H-2-indolecarboxamide (0.312 g, 47%). 1H NMR (DMSO-d6) δ 1.49 (m, 2H), 2.05 (m, 6H), 2.15 (s, 3H), 2.32 (m, 5H), 2.51 (m, 4H), 3.97 (s, 3H), 4.66 (m, 1H), 7.10 (m, 1H), 7.22 (m, 1H), 7.30 (d, J=7.98 Hz, 1H), 8.11 (d, J=8.14 Hz, 1H), 8.24 (s, 1H), 9.44 (s, 1H).

후처리

  1. customSolvent was evaporated
  2. dissolutionthe residue was dissolved in Dichloromethane (5 mL)
  3. waitAfter 30 minutes
  4. filtrationthe solid as 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-222919f28f2545b68e4b15c6eb4aa730
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06921763B2

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