Trifluoroacetic acid → 4-(4-Chloro-2-methoxyphenyl)-1-(9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one hydrochloride

HRID 1020682Notes

Reaction equation

HRID 1020682 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:27][CH2:26][C:25]2[C:24]3[C:19](=[CH:20][C:21]([N:28]4[CH:33]=[CH:32][C:31]([C:34]5[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][C:35]=5[O:41][CH3:42])=[CH:30][C:29]4=[O:43])=[CH:22][CH:23]=3)[N:18]([CH3:44])[C:17]=2[CH2:16]1)=O)(C)(C)C>C(Cl)Cl>[ClH:40].[Cl:40][C:37]1[CH:38]=[CH:39][C:34]([C:31]2[CH:32]=[CH:33][N:28]([C:21]3[CH:20]=[C:19]4[C:24]([C:25]5[CH2:26][CH2:27][NH:15][CH2:16][C:17]=5[N:18]4[CH3:44])=[CH:23][CH:22]=3)[C:29](=[O:43])[CH:30]=2)=[C:35]([O:41][CH3:42])[CH:36]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57950380tert-Butyl-7-(4-(4-chloro-2-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate

Product 1

HCID 686568294-(4-Chloro-2-methoxyphenyl)-1-(9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1.0 mL) was added to a solution of tert-butyl-7-(4-(4-chloro-2-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (0.23 g, 0.44 mmol) in CH2Cl2 (2 mL) under argon and stirred for 1 h. The mixture was concentrated under reduced pressure, and the residue was partitioned between CH2Cl2 and saturated NaHCO3 solution. The organic phase was removed, and the aqueous phase was extracted with CH2Cl2 (10×25 mL). The combined organic extracts were washed with brine (25 mL), dried over Na2SO4, and concentrated under reduced pressure. Flash column chromatography (12 g ISCO CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes to 0:100 over 20 column volumes and hold for 10 column volumes) provided the free base of the title compound. The free base was converted to the HCl salt using 2 N HCl in Et2O as of Example 129 (step b), providing the title compound (0.13 g, 33%) as a yellow solid: mp 294-300° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.43 (br s, 2H), 7.65 (d, J=7.0 Hz, 1H), 7.61 (d, J=1.5 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.44 (d, J=8.5 Hz, 1H), 7.26 (d, J=2.0 Hz, 1H), 7.13 (dd, J=8.5, 2.0 Hz, 1H), 7.09 (dd, J=8.0, 2.0 Hz, 1H), 6.56 (d, J=2.0 Hz, 1H), 6.47 (dd, J=7.0, 1.5 Hz, 1H), 4.49-4.47 (m, 2H), 3.87 (m, 3H), 3.69 (s, 3H), 3.47-3.43 (m, 2H), 3.00-2.97 (m, 2H); ESI MS m/z 420 [M+H]+; HPLC (Method A) 96.7% (AUC), tR=15.5 min.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe residue was partitioned between CH2Cl2 and saturated NaHCO3 solution
  3. customThe organic phase was removed
  4. extractionthe aqueous phase was extracted with CH2Cl2 (10×25 mL)
  5. washThe combined organic extracts were washed with brine (25 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a641abbf9a714219a6ece0406efba3d8
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

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