Sodium Iodide → 5-AMINO-6-CHLORO-2-ETHYL-N-{[1-(3-MORPHOLIN-4-YL-3-OXOPROPYL)PIPERIDIN-4-YL]METHYL}IMIDAZO[1,2-a]PYRIDINE-8-CARBOXAMIDE

HRID 965806노트

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HRID 965806 반응식
[NH2:1][C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][CH3:12])[N:10]=[C:6]2[C:5]([C:13]([NH:15][CH2:16][CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[O:14])=[CH:4][C:3]=1[Cl:23].Cl[CH2:25][CH2:26][C:27]([N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:28].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C)C=O>[NH2:1][C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][CH3:12])[N:10]=[C:6]2[C:5]([C:13]([NH:15][CH2:16][CH:17]2[CH2:22][CH2:21][N:20]([CH2:25][CH2:26][C:27]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[O:28])[CH2:19][CH2:18]2)=[O:14])=[CH:4][C:3]=1[Cl:23]

참가 물질

6

반응물 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 5320543-Chloro-1-(morpholin-4-yl)propan-1-oneHCID 99496125-amino-6-chloro-2-ethyl-N-(piperidin-4-ylmethyl)imidazo[1,2-a]pyridine-8-carboxamide

생성물 1

HCID 100965595-AMINO-6-CHLORO-2-ETHYL-N-{[1-(3-MORPHOLIN-4-YL-3-OXOPROPYL)PIPERIDIN-4-YL]METHYL}IMIDAZO[1,2-a]PYRIDINE-8-CARBOXAMIDE수율 63.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

To a stirred mixture of 5-amino-6-chloro-2-ethyl-N-(piperidin-4-ylmethyl)imidazo[1,2-a]pyridine-8-carboxamide (Example 4, Step 4, 400 mg, 1.19 mmol) and 4-(3-chloro-propanoyl)morpholine (G. Mattalia,; C. Serafini; U. Bucciarelli, Farmaco, Ed. Sci., 1976, 31, 457-67., 529 mg, 2.98 mmol) in N,N-dimethylformamide (5 mL) were added potassium carbonate (576 mg, 4.17 mmol) and sodium iodide (446 mg, 2.98 mmol). After stirring at 90° C. for 48 h, the reaction mixture was cooled to room temperature. The mixture was evaporated and the obtained residue was partitioned between dichloromethane (30 mL) and water (20 mL). The mixture was extracted with dichloromethane (2×30 mL). The combined extract was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. Flash column chromatography (NH-silica gel) of the residue eluting with dichloromethane/methanol (100:1 to 20:1) afforded a yellow amorphous powder, which was crystallized from ethyl acetate/ethanol to give 359 mg (63%) of the title compound as a pale brown solid.

후처리

  1. temperaturethe reaction mixture was cooled to room temperature
  2. customThe mixture was evaporated
  3. customthe obtained residue was partitioned between dichloromethane (30 mL) and water (20 mL)
  4. extractionThe mixture was extracted with dichloromethane (2×30 mL)
  5. extractionThe combined extract
  6. washwas washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. washFlash column chromatography (NH-silica gel) of the residue eluting with dichloromethane/methanol (100:1 to 20:1)
  10. customafforded a yellow amorphous powder, which
  11. customwas crystallized from ethyl acetate/ethanol

출처 및 근거

ORD 기록
ord-2bbb9a8011e743c69c34d30bb829c1fb
출처 데이터셋
uspto-grants-2005_10
특허 번호
US06951867B2

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