2-Propanol, 1-methoxy-2-methyl- → 2-Methoxy-1,1-dimethylethyl 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidine-1-carboxylate

HRID 521234노트

반응식

HRID 521234 반응식
[CH3:1][O:2][CH2:3][C:4]([CH3:7])([OH:6])[CH3:5].ClC(Cl)(O[C:12](=[O:18])OC(Cl)(Cl)Cl)Cl.FC(F)(F)C([O-])=O.[C:27]([C:30]1[C:31]([NH:44][C:45]2[CH:50]=[CH:49][C:48]([F:51])=[CH:47][CH:46]=2)=[N:32][N:33]([C:35]2([CH2:41][C:42]#[N:43])[CH2:40][CH2:39][NH2+:38][CH2:37][CH2:36]2)[CH:34]=1)(=[O:29])[NH2:28]>C1COCC1.C(Cl)Cl>[C:27]([C:30]1[C:31]([NH:44][C:45]2[CH:46]=[CH:47][C:48]([F:51])=[CH:49][CH:50]=2)=[N:32][N:33]([C:35]2([CH2:41][C:42]#[N:43])[CH2:40][CH2:39][N:38]([C:12]([O:6][C:4]([CH3:7])([CH3:5])[CH2:3][O:2][CH3:1])=[O:18])[CH2:37][CH2:36]2)[CH:34]=1)(=[O:29])[NH2:28]

참가 물질

6

반응물 3

HCID 771372-Propanol, 1-methoxy-2-methyl-HCID 94429TriphosgeneHCID 867294014-(4-carbamoyl-3-((4-fluorophenyl)amino)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidin-1-ium 2,2,2-trifluoroacetate2회

생성물 1

HCID 867294072-Methoxy-1,1-dimethylethyl 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidine-1-carboxylate

시약·촉매·용매 2

HCID 6344Dichloromethane용매2회HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 1-methoxy-2-methyl-2-propanol (91 mg, 0.88 mmol) in THF (1.5 mL) and TEA (0.20 mL, 1.4 mmol) was cooled to 0° C. and allowed to stir. Triphosgene (260 mg, 0.876 mmol) was added and the resulting mixture was allowed to warm to ambient temperature and was stirred for 15 minutes. A solution of 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-5) (80 mg, 0.18 mmol) and TEA (0.061 mL, 0.44 mmol) in DCM (1.0 mL) was then added to the reaction mixture dropwise. The resulting mixture was heated to 50° C. and allowed to stir for 16 hours. The solution was cooled to ambient temperature, diluted with DCM, washed with water, dried over anhydrous MgSO4, and concentrated in vacuo. The resulting residue was purified by MPLC on silica gel (using a gradient elution of 0-10% MeOH/DCM) to afford the title compound, Example #28.

후처리

  1. stirringwas stirred for 15 minutes
  2. temperatureThe resulting mixture was heated to 50° C.
  3. stirringto stir for 16 hours
  4. temperatureThe solution was cooled to ambient temperature
  5. washwashed with water
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by MPLC on silica gel (
  9. washa gradient elution of 0-10% MeOH/DCM)

출처 및 근거

ORD 기록
ord-5c26ebc64f024e9f95d70d7e3c383e21
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09328099B2

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