Triethylamine → HCID 53260085, compound

HRID 1992116Notes

Reaction equation

HRID 1992116 reaction equation
Br.[CH3:2][C:3]1[N:7]([CH:8]2[CH2:14][CH:13]3[N:15]([CH2:16][CH2:17][C:18]4([C:24]5[CH:25]=[C:26]([OH:30])[CH:27]=[CH:28][CH:29]=5)[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]4)[CH:10]([CH2:11][CH2:12]3)[CH2:9]2)[C:6]2[CH:31]=[CH:32][CH:33]=[CH:34][C:5]=2[N:4]=1.C(N(CC)CC)C.[Cl:42][C:43]1[CH:51]=[CH:50][C:46]([C:47](O)=[O:48])=[CH:45][C:44]=1[S:52](=[O:55])(=[O:54])[NH2:53].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-:30].[NH4+:4].[Cl:42][C:43]1[CH:51]=[CH:50][C:46]([C:47]([N:21]2[CH2:20][CH2:19][C:18]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=3)([CH2:17][CH2:16][N:15]3[C@H:13]4[CH2:12][CH2:11][C@@H:10]3[CH2:9][CH:8]([N:7]3[C:6]5[CH:31]=[CH:32][CH:33]=[CH:34][C:5]=5[N:4]=[C:3]3[CH3:2])[CH2:14]4)[CH2:23][CH2:22]2)=[O:48])=[CH:45][C:44]=1[S:52]([NH2:53])(=[O:55])=[O:54]

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 68677541HCID 68677541, compound

Product 2

HCID 14923Ammonium HydroxideHCID 53260085HCID 53260085, compoundYield 13.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-4-yl)phenol hydrobromide (0.25 g, 0.48 mmol), triethylamine (0.212 mL, 1.5 mmol) and 4-chloro-3-sulfamoylbenzoic acid (0.113 g, 0.48 mmol) in dimethylformamide (1.5 mL) was treated with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.2 g, 0.53 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 column chromatography on silica gel eluting with 200:15:1 chloroform:methanol:ammonium hydroxide to give 2-chloro-5-[(4-(3-hydroxyphenyl)-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 pink solid (0.022 g, 7%). 1H NMR (400 MHz, CD3OD) δ 8.08 (s, 1H), 7.67 (m, 1H), 7.60 (m, 1H), 7.51 (m, 1H), 7.41 (m, 1H), 7.18 (m, 3H), 6.84 (m, 2H), 6.67 (m, 1H), 4.74 (m, 1H), 4.15 (m, 1H), 3.54 (m, 1H), 3.32 (m, 7H), 2.52 (s, 3H), 2.34-2.50 (m, 3H), 2.20-2.30 (m, 1H), 1.78-2.10 (m, 10H), 1.65-1.72 (m, 2H). HRMS C35H40ClN5O4S m/z 662.2568 (M+H)Cal., 662.2571 (M+H)Obs..

Workup

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

Sources & evidence

ORD record
ord-6cc409db98ad49ada3dc01050ad8e81d
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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