Diisopropylethylamine → 2,4-difluoro-5-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]benzenesulfonic acid

HRID 1992157Notes

Reaction equation

HRID 1992157 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([S:12]([OH:15])(=[O:14])=[O:13])=[CH:7][C:3]=1[C:4]([OH:6])=O.[F:16][C:17]1[CH:18]=[C:19]([C:23]2([CH2:29][CH2:30][N:31]3[CH:36]4[CH2:37][CH2:38][CH:32]3[CH2:33][CH:34]([N:39]3[C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=5[N:41]=[C:40]3[CH3:48])[CH2:35]4)[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH:20]=[CH:21][CH:22]=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>>[F:11][C:9]1[CH:10]=[C:2]([F:1])[C:3]([C:4]([N:26]2[CH2:25][CH2:24][C:23]([C:19]3[CH:20]=[CH:21][CH:22]=[C:17]([F:16])[CH:18]=3)([CH2:29][CH2:30][N:31]3[CH:32]4[CH2:38][CH2:37][CH:36]3[CH2:35][CH:34]([N:39]3[C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=5[N:41]=[C:40]3[CH3:48])[CH2:33]4)[CH2:28][CH2:27]2)=[O:6])=[CH:7][C:8]=1[S:12]([OH:15])(=[O:14])=[O:13]

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 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-benzimidazoleHCID 587279372,4-Difluoro-5-sulfobenzoic acid

Product 1

HCID 587283322,4-difluoro-5-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]benzenesulfonic acidYield 22%

Procedure

Prepared from a mixture of 2,4-difluoro-5-sulfobenzoic acid 885-6b (580 mg, 0.58 mmol, 2 equiv), 1-(8-{2-[4-(3-fluorophenyl)-4-piperidinyl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole (150 mg, 0.29 mmol, 1 equiv), DIEA (260 μL, 1.45 mmol, 5 equiv) and HATU (110 mg, 0.29 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 prep HPLC (HPLC Method C) to afford 2,4-difluoro-5-[(4-(3-fluorophenyl)-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-1-piperidinyl)carbonyl]benzenesulfonic acid (example 885) as a white solid (40 mg, 22% yield).

Workup

  1. customThe crude product was purified by prep HPLC (HPLC Method C)

Sources & evidence

ORD record
ord-713303221cda455fb15699b5f2eea6ac
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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