Potassium Carbonate → HCID 59807784, compound

HRID 383761Notes

Reaction equation

HRID 383761 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([C:11]2[CH:15]=[C:14]([CH3:16])[N:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]([F:26])([F:25])[F:24])[C:12]=2[CH3:27])=[O:10])[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1>CN(C=O)C>[F:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][O:1][C:2]2[CH:3]=[C:4]([NH:8][C:9]([C:11]3[CH:15]=[C:14]([CH3:16])[N:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[C:23]([F:26])([F:24])[F:25])[C:12]=3[CH3:27])=[O:10])[CH:5]=[CH:6][CH:7]=2)=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 680214-Fluorobenzyl bromideHCID 59808031HCID 59808031, compound2×

Product 1

HCID 59807784HCID 59807784, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,5-Dimethyl-1-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (3-hydroxy-phenyl)-amide, previously described in Example 2C, was prepared as a white solid (0.92 g, 80%). 1H-NMR (DMSO-d6): δ 9.15 (1H, s), 9.13 (1H, s), 7.86 (1H, d, J=7.8), 7.77 (1H, t, J=7.3), 7.66 (1H, t, J=7.8), 7.35 (1H, d, J=7.8), 7.20 (1H, t, J=2.0), 6.98 (1H, d, J=8.3), 6.91 (1H, t, J=7.8), 6.47 (1H, s), 6.29 (1H, d, J=7.8), 1.98 (3H, s), 1.73 (3H, s); MS (ESI): 375 (MH+). Into an oven-dried 1 dram vial was added 2,5-dimethyl-1-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (3-hydroxy-phenyl)-amide (50 mg, 133 μmol), K2CO3 (22 mg, 160 μmol), 1-bromomethyl-4-fluoro-benzene (28 mg, 146 μmol) and 0.5 mL DMF. The vial was sealed and stirred 1 h at room temperature. The crude material was purified by reverse-phase chromatography (C18 column), eluting with 0.05% TFA in MeCN/H2O (30:70 to 90:10) to yield the title compound (19 mg, 30%) as an off-white solid. 1H-NMR (DMSO-d6): δ 9.43 (1H, s), 8.00 (1H, d, J=7.8), 7.90 (1H, t, J=7.8), 7.80 (1H, t, J=7.3), 7.58 (1H, m), 7.50 (3H, m), 7.35 (1H, d, J=8.6), 7.22 (3H, m), 6.69 (1H, d, J=8.3), 6.63 (1H, s), 5.07 (2H, s), 2.14 (3H, s), 1.88 (3H, s); MS (ESI): 483 (MH+). B. The following compounds were prepared in a similar manner described in 25A using the appropriate alkyl bromides:

Workup

  1. customThe vial was sealed
  2. customThe crude material was purified by reverse-phase chromatography (C18 column)
  3. washeluting with 0.05% TFA in MeCN/H2O (30:70 to 90:10)

Sources & evidence

ORD record
ord-6ae4a700314544bb805f7ed6ff3d3217
Source dataset
uspto-grants-2013_02
Patent number
US08367667B2

Reaction notes

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