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

HRID 534785Notes

Reaction equation

HRID 534785 reaction equation
[CH3:1][C@H:2]1[CH2:7][N:6]([CH2:8][C:9]2[CH:10]=[N:11][C:12]([NH:15][CH3:16])=[CH:13][CH:14]=2)[CH2:5][CH2:4][N:3]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(N(CC)CC)C.[Cl:31][C:32]1[N:37]=[CH:36][C:35]([C:38](Cl)=[O:39])=[CH:34][CH:33]=1>C(Cl)Cl.O>[Cl:31][C:32]1[N:37]=[CH:36][C:35]([C:38]([N:15]([CH3:16])[C:12]2[N:11]=[CH:10][C:9]([CH2:8][N:6]3[CH2:5][CH2:4][N:3]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[C@@H:2]([CH3:1])[CH2:7]3)=[CH:14][CH:13]=2)=[O:39])=[CH:34][CH:33]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27821656-Chloronicotinoyl ChlorideHCID 592622091,1-Dimethylethyl (2S)-2-methyl-4-{[6-(methylamino)-3-pyridinyl]methyl}-1-piperazinecarboxylate

Product 1

HCID 592622351,1-Dimethylethyl (2S)-4-({6-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]-3-pyridinyl}methyl)-2-methyl-1-piperazinecarboxylateYield 64.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To 1,1-dimethylethyl (2S)-2-methyl-4-{[6-(methylamino)-3-pyridinyl]methyl}-1-piperazinecarboxylate (D96) (0.150 g, 0.469 mmol) and triethylamine (0.098 mL, 0.703 mmol) in DCM (7 mL) under argon was added 6-chloro-3-pyridinecarbonyl chloride (0.099 g, 0.562 mmol). The mixture was stirred at room temperature for 0.3 h then diluted with DCM and water. The organic layer was dried and concentrated to give the crude product which was purified by column chromatography. Elution with EtOAc/DCM gave the title compound as a white colourless gum (0.139 g). δH (CDCl3, 400 MHz) 8.33 (1H, d), 8.19 (1H, d), 7.70 (1H, dd), 7.57 (1H, dd), 7.23 (1H, d), 6.86 (1H, d), 4.20 (1H, br.s), 3.82 (1H, d), 3.58 (3H, s), 3.49 (1H, d), 3.37 (1H, d), 3.08 (1H, td), 2.70 (1H, d), 2.49 (1H, d), 2.16 (1H, dd), 2.04 (1H, m), 1.46 (9H, s), 1.19 (3H, d). MS (ES): MH+ 460/462

Workup

  1. customThe organic layer was dried
  2. concentrationconcentrated
  3. customto give the crude product which
  4. customwas purified by column chromatography
  5. washElution with EtOAc/DCM

Sources & evidence

ORD record
ord-cc26eab7c0e0447e8e77c2c58c4db847
Source dataset
uspto-grants-2014_10
Patent number
US08853218B2

Reaction notes

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