2-Bromo-4-fluorobenzene-1-sulfonyl chloride → methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate

HRID 715964Notes

Reaction equation

HRID 715964 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[CH2:11][CH2:12][CH2:13][CH:6]3[CH2:5][C:4]=2[C:3]=1[C:14]([O:16][CH3:17])=[O:15].[Br:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[S:26](Cl)(=[O:28])=[O:27]>N1C=CC=CC=1.C(Cl)Cl.C(OCC)(=O)C>[Br:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[S:26]([NH:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[CH2:11][CH2:12][CH2:13][CH:6]3[CH2:5][C:4]=2[C:3]=1[C:14]([O:16][CH3:17])=[O:15])(=[O:28])=[O:27]

Participants

6

Reactant 2

HCID 27782162-Bromo-4-fluorobenzene-1-sulfonyl chlorideHCID 86712116methyl 7-amino-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate2×

Product 1

HCID 70984706methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylateYield 39.2%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of methyl 7-amino-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (Intermediate 29, 0.400 g) and 2-bromo-4-fluorobenzenesulfonyl chloride (0.565 g) in pyridine (4 mL) and DCM (12 mL) was stirred at room temperature for 30 minutes. The mixture was diluted with ethyl acetate and washed with aqueous potassium carbonate solution (10%) and brine, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM, with a gradient of 0-2%. The resultant solid was re-purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, containing 1% triethylamine, with a gradient of 0-100% to give a yellow solid which was again purified by chromatography on silica, eluting with a mixture of DCM and cyclohexane (50%), followed by DCM (100%). The resultant solid was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-30%, to give methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (0.317 g) as a yellow gum.

Workup

  1. washwashed with aqueous potassium carbonate solution (10%) and brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was purified by chromatography on silica
  6. washeluting with a mixture of methanol and DCM, with a gradient of 0-2%
  7. customThe resultant solid was re-purified by chromatography on silica
  8. washeluting with a mixture of ethyl acetate and cyclohexane
  9. additioncontaining 1% triethylamine
  10. customwith a gradient of 0-100% to give a yellow solid which
  11. customwas again purified by chromatography on silica
  12. washeluting with a mixture of DCM and cyclohexane (50%)
  13. customThe resultant solid was purified by chromatography on silica
  14. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-30%

Sources & evidence

ORD record
ord-0d7b174cfff2448ba8929fc4267ddf0b
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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