1,1-dimethylethyl (2S)-4-({4-[({4-[(3-fluorophenyl)amino]-1-piperidinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate → 4-[(3-Fluorophenyl)amino]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-1-piperidinecarboxamide

HRID 906379노트

반응식

HRID 906379 반응식
[F:1][C:2]1[CH:3]=[C:4]([NH:8][CH:9]2[CH2:14][CH2:13][N: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])[CH2:11][CH2:10]2)[CH:5]=[CH:6][CH:7]=1>C(Cl)Cl.C(O)(C(F)(F)F)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:8][CH:9]2[CH2:10][CH2:11][N: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])[CH2:13][CH2:14]2)[CH:5]=[CH:6][CH:7]=1

참가 물질

4

반응물 1

HCID 576995151,1-dimethylethyl (2S)-4-({4-[({4-[(3-fluorophenyl)amino]-1-piperidinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

생성물 1

HCID 236344374-[(3-Fluorophenyl)amino]-N-methyl-N-(4-{[(3S)-3-methyl-1-piperazinyl]methyl}phenyl)-1-piperidinecarboxamide수율 80.7%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 6422Trifluoroacetic acid용매

실험 절차

A solution of 1,1-dimethylethyl (2S)-4-({4-[({4-[(3-fluorophenyl)amino]-1-piperidinyl}carbonyl)(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate (D33) (67 mg, 0.124 mmol) in DCM (2.5 ml) and TFA (0.5 ml) was stirred at room temp for ˜1.5 h. The solvent was removed in vacuo and the residue partitioned between DCM and saturated aqueous NaHCO3 solution. The aqueous layer was further extracted with DCM and the combined organic layers were dried and concentrated to give the crude product as a pale yellow oil. Column chromatography eluting with 0-10% (2M NH3 in MeOH)/DCM gave the title compound as a pale yellow oil (44 mg). δH (CDCl3, 400 MHz) 7.27 (2H, d), 7.05 (3H, m), 6.34 (1H, m), 6.29 (1H, m), 6.21 (1H, m), 3.77 (2H, d), 3.62 (1H, d), 3.47 (2H, m), 3.38 (1H, m), 3.21 (3H, s), 2.93 (3H, m), 2.75 (3H, m), 2.20 (1H+H2O, br. s), 2.05 (1H, td), 1.85 (2H, m), 1.72 (1H, m), 1.16 (2H, m), 1.04 (3H, d). MS (ES): MH+ 440.2.

후처리

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between DCM and saturated aqueous NaHCO3 solution
  3. extractionThe aqueous layer was further extracted with DCM
  4. customthe combined organic layers were dried
  5. concentrationconcentrated
  6. customto give the crude product as a pale yellow oil
  7. washColumn chromatography eluting with 0-10% (2M NH3 in MeOH)/DCM

출처 및 근거

ORD 기록
ord-00d1304013ad43cb818417ebaa6b8078
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08012981B2

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