Dimethylformamide → Propyl {(7R)-7-{[(4-fluorophenyl)sulfonyl](methyl)amino}-6,7,8,9-tetrahydro-pyrido[1,2-alpha]indol-10-yl}acetate

HRID 475490Notes

Reaction equation

HRID 475490 reaction equation
[H-].[Na+].[CH3:3]N(C=O)C.[F:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([NH:18][C@H:19]2[CH2:38][N:23]3[C:24]4[C:29]([C:30]([CH2:31][C:32]([O:34][CH2:35][CH2:36][CH3:37])=[O:33])=[C:22]3[CH2:21][CH2:20]2)=[CH:28][CH:27]=[CH:26][CH:25]=4)(=[O:17])=[O:16])=[CH:11][CH:10]=1>[NH4+].[Cl-]>[F:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([N:18]([CH3:3])[C@H:19]2[CH2:38][N:23]3[C:24]4[C:29]([C:30]([CH2:31][C:32]([O:34][CH2:35][CH2:36][CH3:37])=[O:33])=[C:22]3[CH2:21][CH2:20]2)=[CH:28][CH:27]=[CH:26][CH:25]=4)(=[O:16])=[O:17])=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 58399163Propyl (7R)-7-[[(4-fluorophenyl)sulfonyl]amino]-6,7,8,9-tetrahydropyrido[1,2-a]indole-10-acetate

Product 1

HCID 58399166Propyl {(7R)-7-{[(4-fluorophenyl)sulfonyl](methyl)amino}-6,7,8,9-tetrahydro-pyrido[1,2-alpha]indol-10-yl}acetateYield 98%

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (1.05 equiv.) was added to a 0° C. DMF solution (0.14 M) of propyl {(7R)-7-{[(4-fluorophenyl)sulfonyl]amino}-6,7,8,9-tetrahydropyrido [1,2-α]indol-10-yl }acetate from Step 7 and the mixture was stirred at 0 ° C. for 30 min. lodomethane (3 equiv.) was added and the reaction was stirred at 0° C. for 2 h. The mixture was poured in aqueous NH4Cl and extracted with Et2O (2×). The combined organic extracts were washed with water (3×), brine and then dried with MgSO4, filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel using a CombiFlashRF (Teledyne ISCO) eluting with EtOAc/Hex (5:95 to 50:50) to give the title compound (98%) as a colorless oil.

Workup

  1. additionwas added
  2. extractionextracted with Et2O (2×)
  3. washThe combined organic extracts were washed with water (3×), brine
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by column chromatography on silica gel using a CombiFlashRF (Teledyne ISCO)
  8. washeluting with EtOAc/Hex (5:95 to 50:50)

Sources & evidence

ORD record
ord-df32f4b15e954c2f8c007c261b8dcce2
Source dataset
uspto-grants-2014_01
Patent number
US08637541B2

Reaction notes

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