Dichloromethane → 7-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic Acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide Hydrochloride

HRID 335278노트

반응식

HRID 335278 반응식
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([C:20](=[O:32])[NH:21][CH2:22][CH2:23][N:24]4[C@H:29]([CH3:30])[CH2:28][CH2:27][CH2:26][C@@H:25]4[CH3:31])[CH:17]=[CH:16][C:15]=3[F:33])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:34][N:35]1[CH:39]=[C:38](B(O)O)[CH:37]=[N:36]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)[Cl:50]>COCCOC.O>[ClH:50].[CH3:30][C@H:29]1[CH2:28][CH2:27][CH2:26][C@@H:25]([CH3:31])[N:24]1[CH2:23][CH2:22][NH:21][C:20]([C:18]1[CH:17]=[CH:16][C:15]([F:33])=[C:14]([NH:13][C:11]([C:8]2[N:5]3[CH:6]=[CH:7][C:2]([C:38]4[CH:37]=[N:36][N:35]([CH3:34])[CH:39]=4)=[CH:3][C:4]3=[N:10][CH:9]=2)=[O:12])[CH:19]=1)=[O:32]

참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 112635011-Methyl-1H-pyrazole-4-boronic acidHCID 712832197-bromo-N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide2회

생성물 1

HCID 866956747-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic Acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide Hydrochloride

시약·촉매·용매 2

HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

실험 절차

7-Bromo-N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide (Intermediate 4C) (50 mg, 0.097 mmol), 1-methyl-1H-pyrazol-4-ylboronic acid (24.38 mg, 0.194 mmol) and cesium carbonate (126 mg, 0.387 mmol) was dissolved in DME (215 μl)/water (108 μl) to form a solution. Nitrogen was bubbled though the reaction mixture for 2 minutes. PdCl2(dppf).CH2Cl2 adduct (3.95 mg, 4.84 μmol) was added and the mixture was heated using microwave radiation at 100° C. for 15 mins. The water was removed and the organic portion was dry loaded onto silica. The crude product was purified by chromatography on silica eluting with 0-20% 2M NH3 in MeOH and the product fractions were combined and concentrated in vacuo. The product was dissolved in MeOH and passed through a 1 g 2,4,6-trimercaptotriazine silica. The solvent was removed in vacuo and the residue was triturated with ether. The resulting precipitate was filtered and dried in the oven to afford the title compound;

후처리

  1. customto form a solution
  2. customNitrogen was bubbled though the reaction mixture for 2 minutes
  3. temperaturethe mixture was heated
  4. customat 100° C.
  5. customfor 15 mins
  6. customThe water was removed
  7. customthe organic portion was dry
  8. customThe crude product was purified by chromatography on silica eluting with 0-20% 2M NH3 in MeOH
  9. concentrationconcentrated in vacuo
  10. dissolutionThe product was dissolved in MeOH
  11. customThe solvent was removed in vacuo
  12. customthe residue was triturated with ether
  13. filtrationThe resulting precipitate was filtered
  14. customdried in the oven

출처 및 근거

ORD 기록
ord-9c5060acdc5746d390f1f3defa858ed8
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883819B2

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