Hydrochloric Acid → HCID 68289372, compound

HRID 878748Notes

Reaction equation

HRID 878748 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH3:12])=[C:4]([N:13]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][C:36]([F:39])([F:38])[F:37])=[CH:31][CH:30]=2)[S:14]([C:17]2[CH:27]=[CH:26][C:20]([C:21]([O:23]CC)=[O:22])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[N:3]=1.[H-].[Na+].[CH3:42][CH:43]([OH:45])[CH3:44].Cl>O1CCCC1.C(Cl)(Cl)Cl>[CH:43]([O:45][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH3:12])=[C:4]([N:13]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][C:36]([F:38])([F:39])[F:37])=[CH:31][CH:30]=2)[S:14]([C:17]2[CH:18]=[CH:19][C:20]([C:21]([OH:23])=[O:22])=[CH:26][CH:27]=2)(=[O:16])=[O:15])[N:3]=1)([CH3:44])[CH3:42]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 24758Sodium hydrideHCID 86707383HCID 86707383, compound

Product 1

HCID 68289372HCID 68289372, compoundYield 61.6%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of ethyl 4-({(1-bromo-4-methylisoquinolin-3-yl)[4-(trifluoromethoxy)-benzyl]amino}sulfonyl)benzoate (93.5 mg, 0.15 mmol) prepared in Example 9-(1) and sodium hydride (60.0 mg, 1.5 mmol) in tetrahydrofuran (2 mL) was added 2-propanol (0.115 mL, 1.5 mmol) under argon atmosphere, and the mixture was heated to reflux for 4 hours. The mixture was neutralized by 2 mol/L hydrochloric acid, and then thereto was added chloroform. The mixture was stirred, and then separated. The organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methanol/chloroform=2%→10%) to give 4-({(1-isopropoxy-4-methylisoquinolin-3-yl) [4-(trifluoromethoxy)benzyl]amino}sulfonyl)benzoic acid (53.1 mg, 58%) as a brown powder.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 4 hours
  3. customseparated
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (methanol/chloroform=2%→10%)

Sources & evidence

ORD record
ord-dc898ecb65ef4c0e99af845ef3c0dfbf
Source dataset
uspto-grants-2015_03
Patent number
US08987445B2

Reaction notes

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