Triethylamine → HCID 53259749, compound

HRID 1992101Notes

Reaction equation

HRID 1992101 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:5]=[C:6]([C:10]2([CH2:16][CH2:17][N:18]3[C@H:23]4[CH2:24][CH2:25][C@@H:19]3[CH2:20][CH:21]([N:26]3[C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=5[N:28]=[C:27]3[CH3:35])[CH2:22]4)[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:7]=[CH:8][CH:9]=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+:13].[Cl:36][C:37]1[CH:45]=[CH:44][C:40]([C:41]([N:13]2[CH2:12][CH2:11][C:10]([C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([Cl:3])[CH:5]=3)([CH2:16][CH2:17][N:18]3[C@H:19]4[CH2:25][CH2:24][C@@H:23]3[CH2:22][CH:21]([N:26]3[C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=5[N:28]=[C:27]3[CH3:35])[CH2:20]4)[CH2:15][CH2:14]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 25128820HCID 25128820, compound

Product 2

HCID 14923Ammonium HydroxideHCID 53259749HCID 53259749, compoundYield 47.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-((1R,5S)-8-{2-[4-(3-chlorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride (0.15 g, 0.32 mmol), 4-chloro-3-sulfamoylbenzoic acid (0.076 g, 0.32 mmol) and triethylamine (0.14 mL, 1 mmol) in dimethylformamide (1 mL) was treated with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.133 g, 0.35 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 and water, dried and purified by chromatography on silica gel eluting with a 120:15:1 to 60:15:1 gradient of chloroform:methanol:ammonium hydroxide to give 2-chloro-5-[(4-(3-chlorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)carbonyl]benzenesulfonamide as a white solid (0.052 g, 24%). 1H NMR (400 MHz, CD3OD3) δ 8.09 (s, 1H), 7.90 (s, 1H), 7.69 (m, 1H), 7.62 (m, 1H), 7.53 (m, 1H), 7.38-7.46 (m, 3H), 7.27-7.38 (m, 1H), 7.17-7.20 (m, 2H), 4.74 (m, 1H), 4.11 (m, 1H), 3.58 (m, 2H), 3.40 (m, 2H), 3.16-3.22 (m, 1H), 2.54 (s, 3H), 2.41-2.49 (m, 2H), 2.33-2.38 (m, 1H), 2.20-2.26 (m, 1H), 1.94-2.12 (m, 10H), 1.68-1.74 (m, 2H). HRMS C35H39Cl2N5O3S m/z 680.2229 (M+H)Cal., 680.2239 (M+H)Obs..

Workup

  1. customthe resulting precipitate was collected
  2. washwashed with saturated sodium bicarbonate and water
  3. customdried
  4. custompurified by chromatography on silica gel eluting with a 120:15:1 to 60:15:1 gradient of chloroform

Sources & evidence

ORD record
ord-87aa60d7c7784a2d975fe3ba383a0868
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

Loading…