Triethylamine → Propyl (7R)-7-[[(4-fluorophenyl)sulfonyl]amino]-6,7,8,9-tetrahydropyrido[1,2-a]indole-10-acetate

HRID 475489

Reaction equation

HRID 475489 reaction equation
[NH2:1][C@H:2]1[CH2:21][N:6]2[C:7]3[C:12]([C:13]([CH2:14][C:15]([O:17][CH2:18][CH2:19][CH3:20])=[O:16])=[C:5]2[CH2:4][CH2:3]1)=[CH:11][CH:10]=[CH:9][CH:8]=3.[F:22][C:23]1[CH:28]=[CH:27][C:26]([S:29](Cl)(=[O:31])=[O:30])=[CH:25][CH:24]=1.C(N(CC)CC)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:22][C:23]1[CH:28]=[CH:27][C:26]([S:29]([NH:1][C@H:2]2[CH2:21][N:6]3[C:7]4[C:12]([C:13]([CH2:14][C:15]([O:17][CH2:18][CH2:19][CH3:20])=[O:16])=[C:5]3[CH2:4][CH2:3]2)=[CH:11][CH:10]=[CH:9][CH:8]=4)(=[O:31])=[O:30])=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 95884-Fluorobenzenesulfonyl chlorideHCID 58349691(R)-propyl 2-(7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetate

Product 1

HCID 58399163Propyl (7R)-7-[[(4-fluorophenyl)sulfonyl]amino]-6,7,8,9-tetrahydropyrido[1,2-a]indole-10-acetateYield 97%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a CH2Cl2 solution (0.2 M) of propyl ([7R]-7-amino-6,7,8,9-tetrahydro-pyrido[1,2-α]indo1-10-yl)acetate from Step 6 was added 4-fluorobenzenesulfonyl chloride (1.1 equiv.) followed by triethylamine (3 equiv.) and DMAP (1 equiv.). The reaction mixture was stirred for 12 h at rt. The mixture was concentrated under reduced pressure, diluted with EtOAc, and washed with aqueous NaHCO3, water and finally with brine. The organic layer was dried with Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel using a CombiFlashRF (Teledyne ISCO) eluting with EtOAc/Hex (10:90 to 50:50) to give the title compound (97%) as a colorless foam.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additiondiluted with EtOAc
  3. washwashed with aqueous NaHCO3, water and finally with brine
  4. dry with materialThe organic layer was dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel using a CombiFlashRF (Teledyne ISCO)
  8. washeluting with EtOAc/Hex (10:90 to 50:50)

Sources & evidence

ORD record
ord-9eb9697f134b4b07aa6d73718b378104
Source dataset
uspto-grants-2014_01
Patent number
US08637541B2

Linked notes

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