Diisopropylethylamine → 2,4-dichloro-3-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]-N-methylbenzenesulfonamide

HRID 1992148Notes

Reaction equation

HRID 1992148 reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[C:6]([C:10]2([CH2:16][CH2:17][N:18]3[CH:23]4[CH2:24][CH2:25][CH: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.C(N(CC)C(C)C)(C)C.[Cl:45][C:46]1[C:54]([S:55]([NH:58][CH3:59])(=[O:57])=[O:56])=[CH:53][CH:52]=[C:51]([Cl:60])[C:47]=1[C:48](O)=[O:49].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O>[Cl:45][C:46]1[C:47]([C:48]([N:13]2[CH2:12][CH2:11][C:10]([C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([F:3])[CH:5]=3)([CH2:16][CH2:17][N:18]3[CH:23]4[CH2:24][CH2:25][CH: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]2)=[O:49])=[C:51]([Cl:60])[CH:52]=[CH:53][C:54]=1[S:55]([NH:58][CH3:59])(=[O:57])=[O:56]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 290399082,6-Dichloro-3-(methylsulfamoyl)benzoic acidHCID 686759471-(8-{2-[4-(3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride

Product 1

HCID 587277792,4-dichloro-3-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]-N-methylbenzenesulfonamideYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(8-{2-[4-(3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride (100 mg, 0.16 mmol, 1 equiv) and N,N-diisopropylethyl amine (117 μL, 0.66 mmol, 4 equiv) in dimethylformamide (2 mL) was added the mixture of 2,6-dichloro-3-[(methylamino)sulfonyl]benzoic acid 880-1 b. After stirring at RT for several min, O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (62 mg, 0.16 mmol, 1 equiv) was added and the reaction was stirred for 18 h. The mixture was partitioned between dichloromethane and satd. aq. NaHCO3. The organic layer was dried and concentrated and the residue was purified by SiO2 flash column chromatography (100% EtOAc→10% 2M NH3 in MeOH in EtOAC) to provide 2,4-dichloro-3-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]-N-methylbenzenesulfonamide (example 880) as a white solid (25 mg, 22% yield).

Workup

  1. additionwas added
  2. customThe mixture was partitioned between dichloromethane
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customthe residue was purified by SiO2 flash column chromatography (100% EtOAc→10% 2M NH3 in MeOH in EtOAC)

Sources & evidence

ORD record
ord-365466dc69a24683bdaf8e65dad0b667
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

Loading…