Triethylamine → 1,1-Dimethylethyl (2S)-4-({4-[{[6-(3-fluorophenyl)-3-pyridinyl]carbonyl}(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

HRID 534743Notes

Reaction equation

HRID 534743 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14](Cl)=[O:15])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:17][C@H:18]1[CH2:23][N:22]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][CH3:32])=[CH:27][CH:26]=2)[CH2:21][CH2:20][N:19]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].C(N(CC)CC)C>C(Cl)Cl.O>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14]([N:31]([CH3:32])[C:28]3[CH:27]=[CH:26][C:25]([CH2:24][N:22]4[CH2:21][CH2:20][N:19]([C:33]([O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[O:34])[C@@H:18]([CH3:17])[CH2:23]4)=[CH:30][CH:29]=3)=[O:15])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 592621311,1-Dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylateHCID 866181106-(3-Fluorophenyl)-3-pyridinecarbonyl chloride

Product 1

HCID 592621621,1-Dimethylethyl (2S)-4-({4-[{[6-(3-fluorophenyl)-3-pyridinyl]carbonyl}(methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

The acid chloride from step 1 was taken up in DCM and added drop-wise to a mixture of 1,1-dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate (D3) (0.1 g, 0.313 mmol) and triethylamine (0.065 mL, 0.47 mmol) in DCM (5 mL). The reaction mixture was stirred at room temperature under argon for ˜15 h, then diluted with water and DCM. The organic layer was dried and concentrated to give the crude product, which was purified by column chromatography. Elution with EtOAc/petroleum ether yielded the title compound as a yellow oil (0.127 g). δH (CDCl3, 400 MHz) 8.51 (1H, d), 7.75 (1H, dd), 7.67 (2H, m), 7.55 (1H, d), 7.40 (1H, m), 7.24 (2H, d), 7.08 (1H, m), 7.03 (2H, d), 4.15 (1H, br.s), 3.78 (1H, d), 3.53 (3H, s), 3.45 (1H, d), 3.32 (1H, d), 3.06 (1H, td), 2.69 (1H, d), 2.49 (1H, d), 2.09 (1H, dd), 1.98 (1H, m), 1.44 (9H, s), 1.16 (3H, d). MS (ES): MH+ 519.3.

Workup

  1. additionadded drop-wise
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customto give the crude product, which
  5. customwas purified by column chromatography
  6. washElution with EtOAc/petroleum ether

Sources & evidence

ORD record
ord-0a18301c225d4a239e3a1215fee27503
Source dataset
uspto-grants-2014_10
Patent number
US08853218B2

Reaction notes

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