Dimethylacetamide → 6-[(4-Hydroxybenzyl)amino]-2-methylpyrimidine-4-carbonitrile

HRID 1039048Notes

Reaction equation

HRID 1039048 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17]C)=[CH:13][CH:12]=2)[CH:3]=1.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.C[C:49]([N:51](C)C)=O>FC(F)(F)C([O-])=O.[Pd+2].FC(F)(F)C([O-])=O.[Zn].[C-]#N.[Zn+2].[C-]#N>[OH:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][NH:9][C:4]2[N:5]=[C:6]([CH3:8])[N:7]=[C:2]([C:49]#[N:51])[CH:3]=2)=[CH:12][CH:13]=1

Participants

7

Reactant 3

HCID 31374DimethylacetamideHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 624837716-chloro-N-(4-methoxybenzyl)-2-methylpyrimidin-4-amine

Product 1

HCID 669271566-[(4-Hydroxybenzyl)amino]-2-methylpyrimidine-4-carbonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 2733347Palladium(II) trifluoroacetateCatalyst

Conditions

Temperature
95 °C

Procedure

6-chloro-N-(4-methoxybenzyl)-2-methylpyrimidin-4-amine (500 mg, 01.90 mmol) from Step 1 from this example, palladium (II) trifluoroacetate (27.1 mg, 0.082 mmol), zinc dust (23.6 mg, 0.36 mmol), rac-2-(di-t-butylphosphino)-1,1-binaphthyl (66.5 mg, 0.17 mmol), zinc cyanide (125 mg, 1.1 mmol) was added dimethylacetamide (10 mL) in a flask (flame-dried) and evacuated and back-filled with N2 (3×). The reaction was heated to 95° C. for 30 min, cooled to room temperature. Water (20 mL) was added, extracted with ethyl acetate (20 mL), second wash with brine (20 mL). The organic phase was dried by magnesium sulfate and filtered through silica gel pad (1 inch deep), concentrated and purified by column chromatography through a 40 gram RediSep Rf™ silica gel cartridge eluting with 18% ethyl acetate/hexanes to give the title compounds as a pale yellow oil.

Workup

  1. custom(flame-dried)
  2. customevacuated
  3. additionback-filled with N2 (3×)
  4. temperaturecooled to room temperature
  5. additionWater (20 mL) was added
  6. extractionextracted with ethyl acetate (20 mL)
  7. washsecond wash with brine (20 mL)
  8. dry with materialThe organic phase was dried by magnesium sulfate
  9. filtrationfiltered through silica gel pad (1 inch deep)
  10. concentrationconcentrated
  11. custompurified by column chromatography through a 40 gram RediSep Rf™ silica gel cartridge
  12. washeluting with 18% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-974287041ca54e3e8b26127abe3ea4a3
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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