Dimethylformamide → 3-(5-methyl-4-oxo-2-(1-[9-(2-trimethylsilylethoxymethyl)-9H-purin-6-ylamino]ethyl)-4H-quinazolin-3-yl)benzonitrile

HRID 1625146Notes

Reaction equation

HRID 1625146 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:46])[N:5]([C:32]1[CH:33]=[C:34](OS(C(F)(F)F)(=O)=O)[CH:35]=[CH:36][CH:37]=1)[C:6]([CH:12]([NH:14][C:15]1[N:23]=[CH:22][N:21]=[C:20]3[C:16]=1[N:17]=[CH:18][N:19]3[CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[CH3:13])=[N:7]2.[CH3:47][N:48](C=O)C>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.[C-]#N.[Zn+2].[C-]#N>[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:46])[N:5]([C:32]1[CH:33]=[C:34]([CH:35]=[CH:36][CH:37]=1)[C:47]#[N:48])[C:6]([CH:12]([NH:14][C:15]1[N:23]=[CH:22][N:21]=[C:20]3[C:16]=1[N:17]=[CH:18][N:19]3[CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:29])[CH3:31])[CH3:13])=[N:7]2

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 86624483Trifluoromethane sulfonic acid 3-(5-methyl-4-oxo-2-(1-[9-(2-trimethylsilanyl-ethoxymethyl)-9H-purin-6-ylamino]-ethyl)-4H-quinazolin-3-yl)-phenyl ester

Product 1

HCID 666638963-(5-methyl-4-oxo-2-(1-[9-(2-trimethylsilylethoxymethyl)-9H-purin-6-ylamino]ethyl)-4H-quinazolin-3-yl)benzonitrileYield 66%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A 5-mL reaction vial equipped with a magnetic stirrer was charged with compound 138 (200 mg, 0.300 mmol), tetrakis(triphenylphosphine)palladium (34.0 mg, 0.029 mmol), zinc cyanide (70 mg, 0.60 mmol) and anhydrous DMF (1 mL). The vial was purged with nitrogen, heated to 120° C. for 3.5 h then cooled to ambient temperature and poured into a saturated aqueous sodium bicarbonate solution (25 mL). The resulting suspension was extracted with methylene chloride (3×20 mL), and the organic extracts were combined, dried over sodium sulfate and filtered. Concentration of the filtrate followed by purification by column chromatography gave a 66% yield of compound 141 as a white solid. 1H NMR (CDCl3) δ (ppm) 8.30 (d, 1H, J=6.9 Hz), 7.58-8.02 (m, 7H), 7.30 (d, 1H, J=7.0 Hz), 5.60 (s, 2H), 5.07 (bs, 1H), 3.65 (m, 2H), 2.84 (s, 3H), 1.58 (d, 3H, J=6.7 Hz), 0.96 (m, 2H), 0.02 (s, 9H).

Workup

  1. customA 5-mL reaction
  2. customvial equipped with a magnetic stirrer
  3. customThe vial was purged with nitrogen
  4. temperaturethen cooled to ambient temperature
  5. additionpoured into a saturated aqueous sodium bicarbonate solution (25 mL)
  6. extractionThe resulting suspension was extracted with methylene chloride (3×20 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customConcentration of the filtrate followed by purification by column chromatography

Sources & evidence

ORD record
ord-6a432c8e6fff41eabc217fb5bca4ff33
Source dataset
uspto-grants-2014_07
Patent number
US08779131B2

Reaction notes

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