Triethylamine → HCID 53259916, compound

HRID 1992103Notes

Reaction equation

HRID 1992103 reaction equation
Cl.Cl.[CH3:3][C:4]1[N:8]([CH:9]2[CH2:15][CH:14]3[N:16]([CH2:17][CH2:18][C:19]4([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=5[CH3:31])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[CH:11]([CH2:12][CH2:13]3)[CH2:10]2)[C:7]2[CH:32]=[CH:33][CH:34]=[CH:35][C:6]=2[N:5]=1.[Cl:36][C:37]1[CH:45]=[CH:44][C:40]([C:41]([OH:43])=[O:42])=[CH:39][C:38]=1[S:46](=[O:49])(=[O:48])[NH2:47].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O.O>[OH-:42].[NH4+:5].[Cl:36][C:37]1[CH:45]=[CH:44][C:40]([C:41]([N:22]2[CH2:21][CH2:20][C:19]([CH2:18][CH2:17][N:16]3[C@H:11]4[CH2:12][CH2:13][C@@H:14]3[CH2:15][CH:9]([N:8]3[C:7]5[CH:32]=[CH:33][CH:34]=[CH:35][C:6]=5[N:5]=[C:4]3[CH3:3])[CH2:10]4)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[CH3:31])[CH2:24][CH2:23]2)=[O:43])=[CH:39][C:38]=1[S:46]([NH2:47])(=[O:49])=[O:48]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 145684-Chloro-3-sulfamoylbenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68676328HCID 68676328, compound

Product 2

HCID 14923Ammonium HydroxideHCID 53259916HCID 53259916, compoundYield 42.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-methyl-1-(8-{2-[4-(2-methylphenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-1H-benzimidazole dihydrochloride (0.30 g, 0.63 mmol), 4-chloro-3-sulfamoylbenzoic acid (0.15 g, 0.63 mmol) and triethylamine (0.3 mL, 2 mmol) in dimethylformamide (2 mL) was treated with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.26 g, 0.69 mmol) and the resulting mixture was stirred for 1 h at rt. The mixture was diluted with water and the resulting precipitate was collected, washed with saturated sodium bicarbonate solution and water, dried and purified by chromatography on silica gel eluting with a gradient of 310:15:1 to 200:15:1 of chloroform:methanol:ammonium hydroxide to give 2-chloro-5-{[4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-(2-methylphenyl)piperidin-1-yl]carbonyl}benzenesulfonamide as a white solid (0.089 g, 21%). 1H NMR (400 MHz, CD3OD) δ 8.08 (s, 1H), 7.68 (m, 1H), 7.60 (m, 1H), 7.52 (m, 1H), 7.41 (m, 1H), 7.33 (m, 1H), 7.13-7.21 (m, 5H), 4.75 (m, 1H), 4.08 (m, 1H), 3.49-3.58 (m, 2H), 3.31 (m, 5H), 2.55 (m, 7H), 2.46 (m, 3H), 1.90-2.09 (m, 10H), 1.65 (m, 2H). HRMS C36H42ClN5O3S m/z 660.2775 (M+H)Cal., 660.2764 (M+H)Obs..

Workup

  1. customthe resulting precipitate was collected
  2. washwashed with saturated sodium bicarbonate solution and water
  3. customdried
  4. custompurified by chromatography on silica gel eluting with a gradient of 310:15:1 to 200:15:1 of chloroform

Sources & evidence

ORD record
ord-9998157c62764e60a5c12afe849b7439
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

Loading…