Diisopropylethylamine → 4-chloro-N-(1,1-dimethylethyl)-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]benzenesulfonamide

HRID 1992150Notes

Reaction equation

HRID 1992150 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]([CH3:18])([CH3:17])[CH3:16])(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.[F:19][C:20]1[CH:21]=[C:22]([C:26]2([CH2:32][CH2:33][N:34]3[CH:39]4[CH2:40][CH2:41][CH:35]3[CH2:36][CH:37]([N:42]3[C:46]5[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=5[N:44]=[C:43]3[CH3:51])[CH2:38]4)[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:23]=[CH:24][CH:25]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.ClC1C(C(N2CCC(C3C=CC=C(F)C=3)(CCN3C4CCC3CC(N3C5C=CC=CC=5N=C3C)C4)CC2)=O)=C(Cl)C=CC=1S(NC)(=O)=O>>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]([CH3:18])([CH3:17])[CH3:16])(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([N:29]1[CH2:28][CH2:27][C:26]([C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([F:19])[CH:21]=2)([CH2:32][CH2:33][N:34]2[CH:35]3[CH2:41][CH2:40][CH:39]2[CH2:38][CH:37]([N:42]2[C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=4[N:44]=[C:43]2[CH3:51])[CH2:36]3)[CH2:31][CH2:30]1)=[O:6]

Participants

6

Reactant 5

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 257559215-(Tert-butylsulfamoyl)-2-chlorobenzoic acidHCID 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-methylbenzenesulfonamideHCID 587277931-(8-{2-[4-(3-fluorophenyl)-4-piperidinyl]ethyl)-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole

Product 1

HCID 587277134-chloro-N-(1,1-dimethylethyl)-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]benzenesulfonamideYield 35%

Procedure

Prepared from a mixture of 2-chloro-5-{[(1,1-dimethylethyl)amino]sulfonyl}benzoic acid 2b, 1-(8-{2-[4-(3-fluorophenyl)-4-piperidinyl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole (100 mg, 0.16 mmol, 1 equiv), DIEA (117 μL, 0.66 mmol, 4 equiv) and HATU (62 mg, 0.16 mmol, 1 equiv) following the general procedure for 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. The crude product was purified by column chromatography on silica gel eluting with 10% 2M NH3 in methanol in ethyl acetate to afford 4-chloro-N-(1,1-dimethylethyl)-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]benzenesulfonamide as a white solid (40.3 mg, 35% yield).

Workup

  1. customThe crude product was purified by column chromatography on silica gel eluting with 10% 2M NH3 in methanol in ethyl acetate

Sources & evidence

ORD record
ord-80070f2de185472fadac95c2d529a628
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

Loading…