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

HRID 534731Notes

Reaction equation

HRID 534731 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15](Cl)=[O:16])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:18][C@@H:19]1[CH2:24][N:23]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([NH:32][CH3:33])=[CH:28][CH:27]=2)[CH2:22][C@H:21]([CH3:34])[N:20]1[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36].C(N(CC)CC)C>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([N:32]([CH3:33])[C:29]3[CH:28]=[CH:27][C:26]([CH2:25][N:23]4[CH2:24][C@H:19]([CH3:18])[N:20]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C@H:21]([CH3:34])[CH2:22]4)=[CH:31][CH:30]=3)=[O:16])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 592622201,1-Dimethylethyl (2R,6S)-2,6-dimethyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylateHCID 866181086-(4-Fluorophenyl)-2-methyl-3-pyridinecarbonyl chloride

Product 1

HCID 592621651,1-Dimethylethyl (2R,6S)-4-({4-[{[6-(4-fluorophenyl)-2-methyl-3-pyridinyl]carbonyl}(methyl)amino]phenyl}methyl)-2,6-dimethyl-1-piperazinecarboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

The acid chloride from step 1 was taken up in DCM (3 mL) and added to a solution of 1,1-dimethylethyl (2R,6S)-2,6-dimethyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate (D9) (0.23 g, 0.693 mmol) in DCM (2 mL). Triethylamine (0.193 mL, 1.386 mmol) was added and the mixture was stirred overnight at room temperature. 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. The crude product was purified by column chromatography. Elution with 0-50% EtOAc/petroleum yielded the title compound as a white foam (0.331 g). δH (CDCl3, 400 MHz) 7.89 (2H, m), 7.36 (1H, m), 7.26 (1H, m), 7.19 (2H, m), 7.10 (2H, t), 6.99 (2H, m), 4.00 (2H, m), 3.53 (3H, s), 3.34 (2H, s), 2.58 (3H, s), 2.44 (2H, d), 2.05 (2H, m), 1.44 (9H, s), 1.18 (6H, d). MS (ES): MH+ 547.3.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was re-extracted with DCM (×2)
  3. customthe combined organics were dried
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography
  6. washElution with 0-50% EtOAc/petroleum

Sources & evidence

ORD record
ord-fcb11711801e449eaf87dce8ad55f86f
Source dataset
uspto-grants-2014_10
Patent number
US08853218B2

Reaction notes

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