Potassium Carbonate → 4-(benzyloxy)-1-(5-methyl-2-(2-oxo-2-(pyrrolidin-1-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridine-2(1H)-one

HRID 930630Notes

Reaction equation

HRID 930630 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[CH2:28][NH:27][CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:29])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:31][C:32]([N:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1)=[O:33].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[CH2:28][N:27]([CH2:31][C:32](=[O:33])[N:34]5[CH2:38][CH2:37][CH2:36][CH2:35]5)[CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:29])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 884401-(Chloroacetyl)pyrrolidineHCID 44123851HCID 44123851, compound

Product 1

HCID 441950384-(benzyloxy)-1-(5-methyl-2-(2-oxo-2-(pyrrolidin-1-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridine-2(1H)-oneYield 27.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 4-benzyloxy-1-(5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one (100 mg, 0.26 mmol) in DMF (3 mL) was added 2-chloro-1-(pyrrolidin-1-yl)ethanone (77 mg, 0.52 mmol) and K2CO3 (72 mg, 0.52 mmol). The reaction mixture was heated to 70° C. and stirred at 70° C. until the reaction was complete. After it was cooled, the reaction was quenched with water and extracted with CH2Cl2. The organic layer was washed with H2O and 5% LiCl, dried with Na2SO4, filtered, and concentrated. Purification by flash column chromatography (silica gel, 5% CH3OH in CH2Cl2) gave 4-(benzyloxy)-1-(5-methyl-2-(2-oxo-2-(pyrrolidin-1-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridine-2(1H)-one (35 mg, 27%) as a yellow foam. The free base was converted to the HCl salt to the give title compound (30 mg, 80%) as a yellow solid: mp 162-166° C.; 1H NMR (500 MHz, CD3OD) δ 7.60 (d, J=7.5 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.49-7.35 (m, 6H), 7.06 (dd, J=8.5, 1.5 Hz, 1H), 6.33 (dd, J=7.5, 3.0 Hz, 1H), 6.16 (d, J=3.0 Hz, 1H), 5.20 (s, 2H), 4.80 (d, J=14.5 Hz, 1H), 4.54 (d, J=14.5 Hz, 1H), 4.36 (s, 2H), 4.00-3.98 (m, 1H), 3.75 (s, 3H), 3.68-3.65 (m, 1H), 3.54 (t, J=7.0 Hz, 2H), 3.49-3.45 (m, 2H), 3.35-3.33 (m, 2H), 2.05-1.92 (m, 4H); ESI MS m/z 497 [M+H]+; HPLC (Method B) 97.9% (AUC), tR=13.4 min.

Workup

  1. temperatureAfter it was cooled
  2. customthe reaction was quenched with water
  3. extractionextracted with CH2Cl2
  4. washThe organic layer was washed with H2O and 5% LiCl
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash column chromatography (silica gel, 5% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-ddb2aa950bfa4626ae67bb2a9e2a4939
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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