Water → HCID 178426292, compound

HRID 1592612Notes

Reaction equation

HRID 1592612 reaction equation
[CH3:1][C:2]1[C:3]([CH2:8][N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[NH:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[C:32]([C:33](Cl)=[O:34])[C:27]=2[N:26]=[CH:25]1.CCN(CC)CC.O>C(Cl)Cl>[N:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[C:32]([C:33]([N:13]3[CH2:14][CH2:15][CH:10]([N:9]([CH2:16][C:17]4[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=4)[CH2:8][C:3]4[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=4)[CH2:11][CH2:12]3)=[O:34])[C:27]=2[NH:26][CH:25]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 539029101H-benzoimidazole-4-carbonyl chlorideHCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 178426292HCID 178426292, compoundYield 54,655,828%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of COMPOUND 249 (0.100 g, 0.322 nmol) in CH2Cl2 (5 mL) was added 1H-benzoimidazole-4-carbonyl chloride (0.118 g, 0.653 mmol) (White, A. W. et al. J. Med. Chem. 2000, 43, 4084-4097) and Et3N (0.37 g, 0.37 mmol). After the mixture was stirred overnight water (10 mL) was added, and the mixture was extracted with CH2Cl2 (3×20 mL). The extracts were combined and dried over anhydrous Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified by flash chromatography on silica gel columns (column 1, 6:1 EtOAc/MeOH; column 2, 100:5:1 CH2Cl2/MeOH/NH4OH), affording a white solid (0.080 g, 56%). Conversion to the HBr salt using General Procedure D gave a white solid. 1H NMR (D2O) δ 1.55-1.84 (m, 2H), 1.95-1.99 (m, 1H), 2.18-2.22 (m, 1H), 2.45 (s, 6H), 2.88-3.20 (m, 3H), 3.72-3.77 (m, 1H), 4.32 (s, 4H), 4.63-4.70 (m, 1H), 7.61-7.67 (m, 2H), 7.74-7.80 (m, 2H), 7.89-7.93 (m, 1H), 8.28 (d, 2H, J=8.1 Hz), 8.50 (d, 2H, J=5.7 Hz), 9.20 (s, 1H); 13C NMR (D2O) δ 17.41, 27.50, 28.20, 42.48, 47.56, 51.01, 60.02, 117.02, 121.50, 125.51, 126.16, 127.09, 127.71, 131.38, 137.93, 138.77, 140.71, 148.67, 151.08, 167.43. ES-MS m/z 455 (M+Na). Anal. Calcd. for C27H30N6O.3.5HBr.0.25H2O.0.3C4H10O: C, 42.07; H, 5.20; N, 10.44; Br, 34.74. Found: C, 41.86; H, 5.18; N, 10.39; Br, 34.98.

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with CH2Cl2 (3×20 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationAfter filtration the solvent
  5. customwas removed by evaporation under vacuum
  6. customthe residue was purified by flash chromatography on silica gel columns (column 1, 6:1 EtOAc/MeOH; column 2, 100:5:1 CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-bcc01f53b87c4c05a3bfbd5b2f6c831e
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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