Diisopropylethylamine → 2,4-dichloro-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 1992154Notes

Reaction equation

HRID 1992154 reaction equation
[Cl:1][C:2]1[C:10]([S:11]([NH:14][C:15]([CH3:18])([CH3:17])[CH3:16])(=[O:13])=[O:12])=[CH:9][CH:8]=[C:7]([Cl:19])[C:3]=1[C:4]([OH:6])=O.[F:20][C:21]1[CH:22]=[C:23]([C:27]2([CH2:33][CH2:34][N:35]3[CH:40]4[CH2:41][CH2:42][CH:36]3[CH2:37][CH:38]([N:43]3[C:47]5[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=5[N:45]=[C:44]3[CH3:52])[CH2:39]4)[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH:24]=[CH:25][CH:26]=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[C:3]([C:4]([N:30]2[CH2:29][CH2:28][C:27]([C:23]3[CH:24]=[CH:25][CH:26]=[C:21]([F:20])[CH:22]=3)([CH2:33][CH2:34][N:35]3[CH:36]4[CH2:42][CH2:41][CH:40]3[CH2:39][CH:38]([N:43]3[C:47]5[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=5[N:45]=[C:44]3[CH3:52])[CH2:37]4)[CH2:32][CH2:31]2)=[O:6])=[C:7]([Cl:19])[CH:8]=[CH:9][C:10]=1[S:11]([NH:14][C:15]([CH3:18])([CH3:17])[CH3:16])(=[O:13])=[O:12]

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 167715132,6-Dichloro-3-{[(1,1-dimethylethyl)amino]sulfonyl}benzoic 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 587279712,4-dichloro-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 17%

Procedure

Prepared from a mixture of 2,6-dichloro-3-{[(1,1-dimethylethyl)amino]sulfonyl}benzoic acid 884-5a, 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 2,4-dichloro-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 5 as a white solid (21 mg, 17% 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-dd64ee3a34564277ad75352836185aa2
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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