2-Bromo-4-fluorobenzene-1-sulfonyl chloride → Methyl 8-(2-bromo-4-fluorobenzenesulfonylamino)-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate

HRID 595116Notes

Reaction equation

HRID 595116 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]3=[CH:12][CH:13]=[N:14][N:7]3[CH2:6][CH2:5][C:4]=2[C:3]=1[C:15]([O:17][CH3:18])=[O:16].[Br:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[S:27](Cl)(=[O:29])=[O:28]>N1C=CC=CC=1.C(Cl)Cl>[Br:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[S:27]([NH:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]3=[CH:12][CH:13]=[N:14][N:7]3[CH2:6][CH2:5][C:4]=2[C:3]=1[C:15]([O:17][CH3:18])=[O:16])(=[O:29])=[O:28]

Participants

5

Reactant 2

HCID 27782162-Bromo-4-fluorobenzene-1-sulfonyl chloride2×HCID 86712823Methyl 8-amino-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate2×

Product 1

HCID 70984117Methyl 8-(2-bromo-4-fluorobenzenesulfonylamino)-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylateYield 74.3%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of methyl 8-amino-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate (Intermediate 22, 0.060 g) and 2-bromo-4-fluorobenzenesulfonyl chloride (0.081 g) in pyridine (2 mL) and DCM (4 mL) was stirred at room temperature overnight. A further amount of 2-bromo-4-fluoro-benzenesulfonyl chloride (0.010 g) was added and the reaction mixture was stirred at room temperature for 2 hours. The resultant mixture was concentrated in vacuo and the residue was dissolved in DCM and washed with 1M hydrochloric acid, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100% to give methyl 8-(2-bromo-4-fluorobenzenesulfonylamino)-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate (0.088 g) as a glass.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 2 hours
  2. concentrationThe resultant mixture was concentrated in vacuo
  3. dissolutionthe residue was dissolved in DCM
  4. washwashed with 1M hydrochloric acid
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by chromatography on silica
  9. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-100%

Sources & evidence

ORD record
ord-28c7ebc6296d4abaa731905a3c65db85
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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