Triethylamine → 1,1-Dimethylethyl (2S)-4-({4-[[(5-bromo-2-pyridinyl)carbonyl](methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylate

HRID 534754

Reaction equation

HRID 534754 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](Cl)=[O:9])=[N:6][CH:7]=1.[CH3:11][C@H:12]1[CH2:17][N:16]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([NH:25][CH3:26])=[CH:21][CH:20]=2)[CH2:15][CH2:14][N:13]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:25]([CH3:26])[C:22]2[CH:21]=[CH:20][C:19]([CH2:18][N:16]3[CH2:15][CH2:14][N:13]([C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[C@@H:12]([CH3:11])[CH2:17]3)=[CH:24][CH:23]=2)=[O:9])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 190907715-Bromo-pyridine-2-carbonyl chlorideHCID 592621311,1-Dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate

Product 1

HCID 592622381,1-Dimethylethyl (2S)-4-({4-[[(5-bromo-2-pyridinyl)carbonyl](methyl)amino]phenyl}methyl)-2-methyl-1-piperazinecarboxylateYield 97.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

The acid chloride from step 2 (0.801 g, 3.633 mmol) in DCM (10 mL) was added to a solution of 1,1-dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate (D3) (0.928 g, 2.906 mmol) in DCM (20 mL). Triethylamine (1.009 mL, 7.266 mmol) was added and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with DCM and washed with water. The aqueous layer was re-extracted with DCM (×2) and the combined organics were dried and concentrated to give the crude product which was purified by column chromatography. Elution with a 0-50% ethyl acetate/petroleum ether gradient yielded the title compound as a yellow oil (1.432 g). δH (CDCl3, 400 MHz) 8.34 (1H, br.s), 7.72 (1H, br.d), 7.38 (1H, br.d), 7.18 (2H, br.m), 6.98 (2H, br.s), 4.17 (1H, br.s), 3.79 (1H, d), 3.51 (3H, s), 3.46 (1H, d), 3.32 (1H, d), 3.07 (1H, td), 2.68 (1H, d), 2.47 (1H, d), 2.10 (1H, dd), 1.98 (1H, m), 1.45 (9H, s), 1.19 (3H, d). MS (ES): MH+ 503/505.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was re-extracted with DCM (×2)
  3. customthe combined organics were dried
  4. concentrationconcentrated
  5. customto give the crude product which
  6. customwas purified by column chromatography
  7. washElution with a 0-50% ethyl acetate/petroleum ether gradient

Sources & evidence

ORD record
ord-060cf8187e174d2995ced28384c47778
Source dataset
uspto-grants-2014_10
Patent number
US08853218B2

Linked notes

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