Trifluoroacetic acid → HCID 66604402, compound

HRID 2410764Notes

Reaction equation

HRID 2410764 reaction equation
C(O)(C(F)(F)F)=O.[CH3:8][C@H:9]1[CH2:14][N:13]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[N:36]=[C:35]([C:37]5[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[CH:38]=5)[CH:34]=[C:33]([C:47]([O:49][CH3:50])=[O:48])[C:20]=4[N:21](CC4C=CC(OC)=CC=4)[C:22]=3[CH:23]=2)[CH2:12][C@@H:11]([CH3:51])[O:10]1.C1(OC)C=CC=CC=1>>[CH3:51][C@H:11]1[CH2:12][N:13]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[N:36]=[C:35]([C:37]5[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[CH:38]=5)[CH:34]=[C:33]([C:47]([O:49][CH3:50])=[O:48])[C:20]=4[NH:21][C:22]=3[CH:23]=2)[CH2:14][C@@H:9]([CH3:8])[O:10]1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 66604320HCID 66604320, compound

Product 1

HCID 66604402HCID 66604402, compoundYield 75.6%

Conditions

Temperature
60 °C

Procedure

TFA (3 mL) was added to a mixture of methyl 7-((2S,6R)-2,6-dimethylmorpholino)-5-(4-methoxybenzyl)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxylate (27 mg, 0.045 mmol) and anisole (0.049 mL, 0.45 mmol) in a vial. The vial was sealed and heated at 60° C. for 3 hr and then 70° C. for an additional 4 hr. The solvent was removed and the residue was dissolved in EtOAc. This was washed with saturated aqueous NaHCO3 solution, brine, and then dried with sodium sulfate. Removal of the solvents followed by radial chromatography (step gradient elution with DCM containing 50 to 0% hexane followed by 10% EtOAc) to afforded methyl 7-((2S,6R)-2,6-dimethylmorpholino)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxylate (16 mg, 0.034 mmol, 75% yield) as a yellow oil. MS (ESI) m/z 484.1 (M+H). 1H NMR (400 MHz, chloroform-d) d ppm 9.41 (1H, s), 8.42 (1H, s), 8.32 (1H, d, J=7.30 Hz), 8.27 (1H, d, J=8.56 Hz), 8.16 (1H, s), 7.55-7.66 (2H, m), 7.00 (1H, dd, J=8.81, 2.01 Hz), 6.92 (1H, d, J=2.01 Hz), 4.08 (3H, s), 3.85 (2H, ddd, J=10.45, 6.30, 2.39 Hz), 3.63 (2H, d, J=10.58 Hz), 2.51-2.61 (2H, m), 1.30 (6H, d, J=6.04 Hz).

Workup

  1. customThe vial was sealed
  2. customThe solvent was removed
  3. dissolutionthe residue was dissolved in EtOAc
  4. washThis was washed with saturated aqueous NaHCO3 solution, brine
  5. dry with materialdried with sodium sulfate
  6. customRemoval of the solvents
  7. washfollowed by radial chromatography (step gradient elution with DCM containing 50 to 0% hexane followed by 10% EtOAc)

Sources & evidence

ORD record
ord-2519848ab1b2437baee26a6cae9ce0d3
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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