Dimethylformamide → 7-chloro-1-oxo-2,5-dihydro-1H-pyrido[4,3-b]indole-4-carbonitrile

HRID 1970992Notes

Reaction equation

HRID 1970992 reaction equation
Br[C:2]1[C:7]2[NH:8][C:9]3[CH:10]=[C:11]([Cl:15])[CH:12]=[CH:13][C:14]=3[C:6]=2[C:5](=[O:16])[NH:4][CH:3]=1.[CH3:17][N:18](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:15][C:11]1[CH:12]=[CH:13][C:14]2[C:6]3[C:5](=[O:16])[NH:4][CH:3]=[C:2]([C:17]#[N:18])[C:7]=3[NH:8][C:9]=2[CH:10]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 565950584-bromo-7-chloro-5H-pyrido[4,3-b]indol-1-ol

Product 1

HCID 565951917-chloro-1-oxo-2,5-dihydro-1H-pyrido[4,3-b]indole-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst2×

Conditions

Temperature
90 °C

Procedure

4-Bromo-7-chloro-2,5-dihydro-1H-pyrido[4,3-b]indol-1-one (35.55 g, 119 mmol), zinc cyanide (9.82 g, 84 mmol), and Pd(PPh3)4 (13.81 g, 11.95 mmol) were combined and stored under vacuum for 20 min before DMF (300 mL, presparged with nitrogen for 1 h) was transferred to the mixture via cannula. The reaction mixture was heated to 90° C. overnight. Additional Pd(PPh3)4 (13.0 g, 11.2 mmol) was added to the mixture, and the resultant mixture was heated to 90° C. for 20 h, cooled to room temperature, and left to stir for 1 d. The reaction mixture was filtered, and washed with DMF. The filtrate was treated with water (15 mL), aged at room temperature for 3 h, treated with additional water (70 mL), and the resultant slurry was left overnight. The mixture was treated with additional water (70 mL), filtered, washed with water, and dried under vacuum. The solid was suspended in EtOAc, aged, filtered, washed with EtOAc, and dried under vacuum to give the title compound. 1H NMR (600 MHz, CD3SOCD3) δ 12.66 (s, 1H); 12.19 (s, 1H); 8.31 (s, 1H); 8.06 (d, 1H); 7.55 (s, 1H); 7.30 (d, 1H). LRMS (APCI) calc'd for (C12H6ClN3O) [M+H]+, 244.0. found 244.0.

Workup

  1. temperaturecooled to room temperature
  2. waitleft
  3. filtrationThe reaction mixture was filtered
  4. washwashed with DMF
  5. additionThe filtrate was treated with water (15 mL)
  6. waitaged at room temperature for 3 h
  7. additiontreated with additional water (70 mL)
  8. waitthe resultant slurry was left overnight
  9. additionThe mixture was treated with additional water (70 mL)
  10. filtrationfiltered
  11. washwashed with water
  12. customdried under vacuum
  13. filtrationfiltered
  14. washwashed with EtOAc
  15. customdried under vacuum

Sources & evidence

ORD record
ord-8e17282788324777b513e4bd92baf70f
Source dataset
uspto-grants-2013_04
Patent number
US08431569B2

Reaction notes

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