Dimethylformamide → HCID 21102146, compound

HRID 1353595Notes

Reaction equation

HRID 1353595 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[N:6]([CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)[CH2:5]2.[CH3:19][N:20](C)C=O>[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>[O:12]=[C:7]1[N:6]([CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH2:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:19]#[N:20])[CH:3]=2)[NH:8]1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 21102206HCID 21102206, compound

Product 1

HCID 21102146HCID 21102146, compoundYield 38%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

6-Bromo-3-piperidin-4-yl-3,4-dihydro-1H-quinazolin-2-one (0.16 g, 0.52 mmol), zinc cyanide (37 mg, 0.31 mmol) and tetrakis(triphenylphosphine)palladium(0) (60 mg, 0.05 mmol) were combined in dimethylformamide (4 mL). The reaction flask was connected to high vacuum and degassed (3×) by a freeze-thawing method, before being heated at 90° C. with stirring under nitrogen for 1 h. After cooling to room temperature, the solution was evaporated in vacuo and the crude mixture purified by preparative HPLC to afford 50 mg (38%) of the desired nitrile. 1H-NMR (CD3OD) δ 1.99 (m, 2H), 2.08–2.23 (m, 2H), 3.15 (m, 2H), 3.50 (bs, 1H), 3.55 (bs, 1H), 4.40 (m, 1H), 4.47 (s, 2H), 6.93 (d, J=8.1, 1H), 4.10 (m, 2H). Mass spec.: 257.13 (MH)+.

Workup

  1. customdegassed (3×) by a freeze-thawing method
  2. temperatureAfter cooling to room temperature
  3. customthe solution was evaporated in vacuo
  4. customthe crude mixture purified by preparative HPLC

Sources & evidence

ORD record
ord-2998d2defcea4e939a3e13785ff8a6c9
Source dataset
uspto-grants-2007_05
Patent number
US07220862B2

Reaction notes

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