Triethylamine → Taladegib

HRID 2389249Notes

Reaction equation

HRID 2389249 reaction equation
[CH3:1][NH:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:19]3[N:23]([CH3:24])[N:22]=[CH:21][CH:20]=3)=[N:11][N:10]=2)[CH2:5][CH2:4]1.C(N(CC)CC)C.[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](Cl)=[O:38])=[C:35]([C:42]([F:45])([F:44])[F:43])[CH:34]=1>C(Cl)Cl>[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37]([N:2]([CH3:1])[CH:3]2[CH2:4][CH2:5][N:6]([C:9]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[C:12]([C:19]4[N:23]([CH3:24])[N:22]=[CH:21][CH:20]=4)=[N:11][N:10]=3)[CH2:7][CH2:8]2)=[O:38])=[C:35]([C:42]([F:45])([F:44])[F:43])[CH:34]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 6056804-Fluoro-2-(trifluoromethyl)benzoyl chlorideHCID 59627388N-methyl-1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-amine

Product 1

HCID 49848070TaladegibYield 86.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Treat a solution of N-methyl-1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-amine (2.8 g, 8.68 mmol) and triethylamine (3.36 mL, 26 1 mmol) in CH2Cl2 (30 mL) with 4-fluoro-2-(trifluoromethyl)benzoyl chloride (2.14 mL, 10.42 mmol). Stir for 3 h at ambient temperature. Concentrate the reaction mixture under reduced pressure. Purify the resulting residue by flash silica gel chromatography (hexane:ethyl acetate:2 M NH3 in MeOH=20:5:1) to provide the free base as a yellow foam (3.83 g, 86%). ES/MS m/z 513.0 (M+1).

Workup

  1. concentrationConcentrate the reaction mixture under reduced pressure
  2. customPurify the resulting residue by flash silica gel chromatography (hexane:ethyl acetate:2 M NH3 in MeOH=20:5:1)

Sources & evidence

ORD record
ord-91b2f0cf25614379b05004e95f3bf653
Source dataset
uspto-grants-2012_09
Patent number
US08273742B2

Reaction notes

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