Triethylamine → HCID 53259584, compound

HRID 1992109Notes

Reaction equation

HRID 1992109 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]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=5)[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:35]=[CH:36][CH:37]=[CH:38][C:6]=2[N:5]=1.C(N(CC)CC)C.[NH2:46][S:47]([C:50]1[CH:51]=[C:52]([CH:56]=[CH:57][C:58]=1[Cl:59])[C:53](Cl)=[O:54])(=[O:49])=[O:48]>ClCCl>[Cl:59][C:58]1[CH:57]=[CH:56][C:52]([C:53]([N:22]2[CH2:23][CH2:24][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:35]=[CH:36][CH:37]=[CH:38][C:6]=5[N:5]=[C:4]3[CH3:3])[CH2:10]4)([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:33])([F:32])[F:34])[CH:26]=3)[CH2:20][CH2:21]2)=[O:54])=[CH:51][C:50]=1[S:47]([NH2:46])(=[O:49])=[O:48]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 30179793-(Aminosulfonyl)-4-chlorobenzoyl chlorideHCID 68676595HCID 68676595, compound

Product 1

HCID 53259584HCID 53259584, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-methyl-1-[8-(2-{4-[3-(trifluoromethyl)phenyl]piperidin-4-yl}ethyl)-8-azabicyclo[3.2.1]oct-3-yl]-1H-benzimidazole dihydrochloride (0.1 g, 0.2 mmol), triethylamine (0.056 mL, 0.4 mmol) and 3-(aminosulfonyl)-4-chlorobenzoyl chloride (0.056 g, 0.22 mmol) in dichloromethane (2 mL) was stirred at rt for 1.5 h. The reaction mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate solution, dried, concentrated and purified by three successive chromatographies on silica gel eluting with mixtures of methanol in dichloromethane 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-[3-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)benzenesulfonamide as a wax (0.002 g, 2%). 1H NMR (400 MHz, CD3OD3) δ 7.79-7.94 (m, 2H), 7.57-7.71 (m, 5H), 7.40-7.54 (m, 2H), 7.15-7.21 (m, 2H), 4.73 (m, 1H), 4.15 (m, 1H), 3.39-3.55 (m, 4H), 3.16-3.22 (m, 1H), 2.52 (s, 3H), 2.34-2.50 (m, 3H), 2.22-2.32 (m, 1H), 1.94-2.12 (m, 10H), 1.68-1.74 (m, 2H). HRMS C36H39ClF3N5O3S m/z 714.2492 (M+H)Cal., 714.2496 (M+H)Obs..

Workup

  1. washwashed with saturated sodium bicarbonate solution
  2. customdried
  3. concentrationconcentrated
  4. custompurified by three successive chromatographies on silica gel eluting with mixtures of methanol in dichloromethane

Sources & evidence

ORD record
ord-caaea12d1c04489fb4f7fe0fbd9a8a20
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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