Dimethylformamide → 1-(2-aminopyrimidin-4-yl)-1H-1,3-benzodiazole-6-carbonitrile

HRID 1398506Notes

Reaction equation

HRID 1398506 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C:10]3[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=3)[C:6]=2[CH:17]=1.[Cl-].[NH4+].[CH3:20][N:21](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>[NH2:16][C:12]1[N:11]=[C:10]([N:7]2[C:6]3[CH:17]=[C:2]([C:20]#[N:21])[CH:3]=[CH:4][C:5]=3[N:9]=[CH:8]2)[CH:15]=[CH:14][N:13]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 681819584-(6-bromo-1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine

Product 1

HCID 681835231-(2-aminopyrimidin-4-yl)-1H-1,3-benzodiazole-6-carbonitrile

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a round bottom flask equipped with a condenser and nitrogen bubbler attached to a bleach scrubber bath was added 4-(6-bromo-1H-1,3-benzodiazol-1-yl)pyrimidin-2-amine (90% purity, 83 mg, 0.26 mmol) and zinc cyanide (30.23 mg, 0.26 mmol) in de-gassed DMF (2 mL). Tetrakis(triphenylphosphine)palladium (29.75 mg, 0.03 mmol) was then added and the reaction heated stirred at 100° C. under nitrogen for 30 min. The reaction mixture was allowed to cool to RT and poured into saturated aqueous ammonium chloride (6 mL) and extracted into DCM (×2). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. The residue was combined with the precipitate formed during the aqueous work up process and was purified by flash chromatography (Isolute column, 10% MeOH in DCM) to afford the title compound as a pale beige solid; 1H NMR (500 MHz, DMSO) δ 6.90-7.42 (3H, m), 7.76 (1H, dd, J=8.35, 1.58 Hz), 7.94 (1H, d, J=8.04 Hz), 8.40 (1H, d, J=5.52 Hz), 9.20 (1H, d, J=0.95 Hz), 9.33 (1H, s); LC-MS: m/z=+236.95 (M+H)+.

Workup

  1. customTo a round bottom flask equipped with a condenser
  2. customnitrogen bubbler attached to a bleach scrubber bath
  3. temperaturethe reaction heated
  4. temperatureto cool to RT
  5. extractionextracted into DCM (×2)
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customformed during the aqueous work up process
  10. customwas purified by flash chromatography (Isolute column, 10% MeOH in DCM)

Sources & evidence

ORD record
ord-905c9dfde48843d6ae73a8325939de33
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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