Potassium Cyanide → 2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetonitrile

HRID 1473259Notes

Reaction equation

HRID 1473259 reaction equation
[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]3[C:16]([C:24]4[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=4)=[C:17]([CH2:22]O)[N:18]([CH3:21])[C:19](=[O:20])[C:8]2=3)=[CH:4][CH:3]=1.S(Br)(Br)=O.[C-:37]#[N:38].[K+]>[Cl-].[Na+].O>[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]3[C:16]([C:24]4[CH:25]=[CH:26][C:27]([CH3:30])=[CH:28][CH:29]=4)=[C:17]([CH2:22][C:37]#[N:38])[N:18]([CH3:21])[C:19](=[O:20])[C:8]2=3)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 9032Potassium CyanideHCID 68176Thionyl bromideHCID 894631249-(4-fluorobenzyl)-3-(hydroxymethyl)-2-methyl-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-1-one

Product 1

HCID 894629402-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetonitrileYield 86.3%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 9-(4-fluorobenzyl)-3-(hydroxymethyl)-2-methyl-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-1-one (125 mg, 0.293 mmol) 1,2-Dichloroethane (DCE) (3 mL) was treated with Thionyl bromide (0.022 mL, 0.293 mmol), heated at 70° C. for 2 hours and then concentrated to dryness. The resultant was dissolved in DMF (2 mL), treated with KCN (76 mg, 1.17 mmol) and then stirred at room temperature overnight. Brine was added and the mixture was extracted with ethyl acetate. The combined extracts were dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-70% ethyl acetate/hexanes) to afford 2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetonitrile (110 mg, 0.253 mmol, 86% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.29-7.44 (m, 4H) 7.17-7.24 (m, 1H) 6.91-6.99 (m, 4H) 6.62-6.70 (m, 1H) 6.10-6.16 (m, 2H) 3.90 (s, 3H) 3.67 (s, 2H) 2.51 (s, 3H); LCMS (m/z) ES+=436 (M+1).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe resultant was dissolved in DMF (2 mL)
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe combined extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel (0-70% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-29be9ffe0df541e2b1690e2043e5ea19
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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