Trifluoroacetic acid → 6-[(4-Fluorophenyl)oxy]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-3-pyridinecarboxamide

HRID 534799노트

반응식

HRID 534799 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([N:17]([CH3:39])[C:18]3[CH:23]=[CH:22][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[C@@H:27]([CH3:38])[CH2:26]4)=[CH:20][CH:19]=3)=[O:16])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([N:17]([CH3:39])[C:18]3[CH:23]=[CH:22][C:21]([CH2:24][N:25]4[CH2:30][CH2:29][NH:28][C@@H:27]([CH3:38])[CH2:26]4)=[CH:20][CH:19]=3)=[O:16])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 592621161,1-Dimethylethyl (2S)-4-({4-[({6-[(4-fluorophenyl)oxy]-3-pyridinyl}carbonyl) (methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

생성물 1

HCID 237290236-[(4-Fluorophenyl)oxy]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-3-pyridinecarboxamide수율 89.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

1,1-Dimethylethyl (2S)-4-({4-[({6-[(4-fluorophenyl)oxy]-3-pyridinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (D16) (0.518 g, 0.97 mmol) was dissolved in DCM (19.2 mL) and TFA (4.8 mL) added. The solution was stirred for 1.5 h then the solvent was removed in vacuo. The product was taken up in methanol and eluted through an SCX (10 g) column with 2M NH3 in methanol solution. The solvent was removed to give a colourless oil which was purified by column chromatography. Elution with a 0-5% (2M NH3 in methanol)/DCM gradient yielded the title compound as a colourless oil (0.379 g). δH (CDCl3, 400 MHz) 8.07 (1H, dd), 7.65 (1H, dd), 7.22 (2H, d), 7.04 (6H, m), 6.70 (1H, d), 3.48 (3H, s), 3.43 (2H, s), 3.13 (br.s), 2.95 (3H, m), 2.70 (2H, d), 2.04 (1H, m), 1.74 (1H, m), 1.05 (3H, d). MS (ES): MH+ 435.3.

후처리

  1. customthe solvent was removed in vacuo
  2. washeluted through an SCX (10 g) column with 2M NH3 in methanol solution
  3. customThe solvent was removed
  4. customto give a colourless oil which
  5. customwas purified by column chromatography
  6. washElution with a 0-5% (2M NH3 in methanol)/DCM gradient

출처 및 근거

ORD 기록
ord-7bf6236aa01a4b939eaec14d03330c4d
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08853218B2

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