tert-Butanol → 1-{3-[4-(2-Chloro-6-methanesulfonylamino-phenyl)-piperazin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-sulfonic acid amide

HRID 734136Notes

Reaction equation

HRID 734136 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH2:27][CH2:28][CH2:29][N:30]3[CH2:35][CH2:34][N:33]([C:36]4[C:41]([NH:42][S:43]([CH3:46])(=[O:45])=[O:44])=[CH:40][CH:39]=[CH:38][C:37]=4[Cl:47])[CH2:32][CH2:31]3)[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[C:10]=2[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.Cl[S:56]([N:59]=C=O)(=[O:58])=[O:57].CC(O)(C)C>C(Cl)Cl.CO.C(Cl)Cl>[Cl:47][C:37]1[CH:38]=[CH:39][CH:40]=[C:41]([NH:42][S:43]([CH3:46])(=[O:44])=[O:45])[C:36]=1[N:33]1[CH2:34][CH2:35][N:30]([CH2:29][CH2:28][CH2:27][N:14]2[C:11]3[CH2:12][CH2:13][N:8]([S:56]([NH2:59])(=[O:58])=[O:57])[CH2:9][C:10]=3[C:16]([C:17]3[CH:18]=[CH:19][C:20]([C:23]([F:26])([F:24])[F:25])=[CH:21][CH:22]=3)=[N:15]2)[CH2:31][CH2:32]1

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 6422Trifluoroacetic acidHCID 70918Chlorosulfonyl isocyanateHCID 684622321-{3-[4-(2-Chloro-6-methanesulfonylamino-phenyl)-piperazin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 101465191-{3-[4-(2-Chloro-6-methanesulfonylamino-phenyl)-piperazin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-sulfonic acid amideYield 88.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 97 mg (0.14 mmol) of 1-{3-[4-(2-chloro-6-methanesulfonylamino-phenyl)-piperazin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester in 3 mL of CH2Cl2 was treated with 1.5 mL of trifluoroacetic acid. The reaction mixture was stirred at 25° C. for 1 h before all volatiles were removed. To this crude material in 0.5 mL of CH2Cl2 was added dropwise a premixed solution of chlorosulfonyl isocyanate (18 μL, 0.209 mmol) and 2-methyl-2-propanol (20 μL, 0.209 mmol) in CH2Cl2 (0.150 mL). The reaction mixture was allowed to stir at 25° C. overnight. Preparative TLC (silica, 2-10% MeOH/CH2Cl2) provided the title compound (84 mg, 78%). TLC (silica, 10% MeOH/CH2Cl2): Rf=0.3. MS (electrospray): exact mass calculated for C32H41ClF3N7O6S2, 775.22; m/z found, 776.2 [M+H]+.

Workup

  1. customwere removed
  2. stirringto stir at 25° C. overnight

Sources & evidence

ORD record
ord-506ecc34a21645d6b139ef317fd0baf5
Source dataset
uspto-grants-2009_09
Patent number
US07589202B2

Reaction notes

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