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 883800ノート

反応式

HRID 883800 の反応式
[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

参加物

4

反応物 1

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 6422Trifluoroacetic acid溶媒

実験手順

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. This whole was dissolved in DCM and treated with 1M HCl in Et2O (100 ul). The solvent was removed in vacuo to give the hydrochloride salt of the title compound as a white solid (47 mg). MS (ES): MH+ 440.2.

後処理

  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

出典と根拠

ORDレコード
ord-6700c71116db4cab91043acf95883b84
出典データセット
uspto-grants-2012_08
特許番号
US08236953B2

反応ノート

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