tert-Butanol → 1-{3-[4-(3-Methyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-sulfonic acid amide

HRID 1371005Notes

Reaction equation

HRID 1371005 reaction equation
Cl[S:2]([N:5]=C=O)(=[O:4])=[O:3].CC(O)(C)C.[CH3:13][N:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]([CH:23]2[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][CH2:31][N:32]3[C:40]4[CH2:39][CH2:38][NH:37][CH2:36][C:35]=4[C:34]([C:41]4[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][CH:42]=4)=[N:33]3)[CH2:25][CH2:24]2)[C:15]1=[O:51].C(N(CC)CC)C>C(Cl)Cl.CO.C(Cl)Cl>[CH3:13][N:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]([CH:23]2[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][CH2:31][N:32]3[C:40]4[CH2:39][CH2:38][N:37]([S:2]([NH2:5])(=[O:4])=[O:3])[CH2:36][C:35]=4[C:34]([C:41]4[CH:42]=[CH:43][C:44]([C:47]([F:49])([F:50])[F:48])=[CH:45][CH:46]=4)=[N:33]3)[CH2:25][CH2:24]2)[C:15]1=[O:51]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 222937351-Methyl-3-(1-{3-[3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-one

Product 1

HCID 102327321-{3-[4-(3-Methyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-sulfonic acid amideYield 108.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of chlorosulfonyl isocyanate (0.018 mL, 0.209 mmol) in CH2Cl2 (0.150 mL) was added 2-methyl-2-propanol (0.020 mL, 0.209 mmol) and the solution was stirred at room temperature for 15 min. This solution was then added dropwise to a solution of 1-methyl-3-(1-{3-[3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-1,3-dihydro-benzoimidazol-2-one (75 mg, 0.139 mmol) and triethylamine (0.039 mL, 0.279 mmol) in CH2Cl2 (0.4 mL). An additional 0.15 mL of CH2Cl2 was used to transfer all of the material to the reaction mixture. The reaction mixture was allowed to stir overnight. Column chromatography (silica, 2-10% MeOH/CH2Cl2) gave 93 mg (93%) of the title compound. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.24. MS (electrospray): calculated for C34H42F3N7O5S, 718.3 ([M+H]+); m/z found, 718.3.

Workup

  1. stirringto stir overnight

Sources & evidence

ORD record
ord-59396ecf18b04fc6bdc99284dfdb4ce0
Source dataset
uspto-grants-2003_06
Patent number
US06583155B2

Reaction notes

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