Pyrrolidine → 4-(Benzyloxy)-1-(5-methyl-2-(2-(pyrrolidin-1-yl)acetyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one dihydrochloride

HRID 1020528Notes

Reaction equation

HRID 1020528 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][N:27]([C:29](=[O:32])[CH2:30][Cl:31])[CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:33])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1>CC#N>[ClH:31].[ClH:31].[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]([C:29](=[O:32])[CH2:30][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:33])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 579503694-(Benzyloxy)-1-(2-(2-chloroacetyl)-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one

Product 1

HCID 686574444-(Benzyloxy)-1-(5-methyl-2-(2-(pyrrolidin-1-yl)acetyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one dihydrochlorideYield 173.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-(Benzyloxy)-1-(2-(2-chloroacetyl)-5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one (70 mg, 0.15 mmol) was dissolved in MeCN (0.5 mL) and pyrrolidine (54 mg, 0.76 mmol) was added. The reaction mixture was refluxed for 2 h, concentrated and the residue purified by preparative HPLC. The fractions were concentrated, and the residue was converted to the free base by partitioning between CH2Cl2 and sat. Na2CO3 solution. The organic phase was removed, and the aqueous layer was extracted with CH2Cl2. The combined organic extracts were dried over Na2SO4, filtered and concentrated to dryness. Conversion to the HCl salt (2 N HCl/Et2O) provided the title compound (74 mg, 97%) as a beige solid: 1H NMR (500 MHz, CD3OD) δ 7.62 (dd, J=7.7, 1.9 Hz, 1H), 7.53 (d, J=8.0 Hz, 1H) 7.46-7.44 (m, 2H), 7.41-7.35 (m, 4H), 7.06 (dd, J=8.0, 1.7 Hz, 1H), 6.36 (d, J=7.6 Hz, 1H), 6.18 (s, 1H), 5.25 (s, 2H), 4.90 (m, 1H, masked by solvent), 4.82 (s, 1H), 4.53 (d, J=14.2 Hz, 2H), 4.09 (t, J=6.5 Hz, 1H), 3.91 (t, J=6.4 Hz, 1H), 3.89-3.86 (m, 2H), 3.77 (s, 3H), 3.20-3.18 (m, 2H), 3.05-3.03 (m, 1H), 2.99-2.97 (m, 1H), 2.12-2.10 (m, 2H), 2.08-2.05 (m, 2H); ESI MS m/z 497 [M+H]+; HPLC (Method B) 95.0% (AUC), tR=13.1 min.

Workup

  1. temperatureThe reaction mixture was refluxed for 2 h
  2. concentrationconcentrated
  3. customthe residue purified by preparative HPLC
  4. concentrationThe fractions were concentrated
  5. customby partitioning between CH2Cl2 and sat. Na2CO3 solution
  6. customThe organic phase was removed
  7. extractionthe aqueous layer was extracted with CH2Cl2
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-c54743c56fce431fa29eac982a00a960
Source dataset
uspto-grants-2014_05
Patent number
US08716308B2

Reaction notes

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