Water → Methyl 4-cyano-2-(4-ethylpiperazin-1-yl)-6-(m-tolylamino)pyrimidine-5-carboxylate

HRID 515967Notes

Reaction equation

HRID 515967 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([NH:12][C:13]2[CH:14]=[C:15]([CH3:19])[CH:16]=[CH:17][CH:18]=2)[N:5]=[C:4]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH3:27])[CH2:22][CH2:21]2)[N:3]=1.O.[CH3:29][N:30](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>[C:29]([C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([NH:12][C:13]2[CH:14]=[C:15]([CH3:19])[CH:16]=[CH:17][CH:18]=2)[N:5]=[C:4]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH3:27])[CH2:22][CH2:21]2)[N:3]=1)#[N:30]

Participants

6

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 58317524Methyl 4-chloro-2-(4-ethylpiperazin-1-yl)-6-(m-tolylamino)pyrimidine-5-carboxylate

Product 1

HCID 58317563Methyl 4-cyano-2-(4-ethylpiperazin-1-yl)-6-(m-tolylamino)pyrimidine-5-carboxylateYield 34%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

A mixture of methyl 4-chloro-2-(4-ethylpiperazin-1-yl)-6-(m-tolylamino)pyrimidine-5-carboxylate (152.6 mg, 0.391 mmol), tetrakis(triphenylphosphine)palladium (40.8 mg, 0.035 mmol) and zinc(II) cyanide (25.2 mg, 0.215 mmol) in DMF (3 mL) was stirred at 90° C. for 3 h. Water was added and the resulting mixture was extracted with EtOAc. The organic layers were washed with aq NaHCO3, water, and brine, were dried over anhydrous Na2SO4, and then filtered through SiO2. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (SiO2 hexanes/EtOAc=5/1) to give the title compound as a yellow oil (51.1 mg, 34%). 1H NMR (500 MHz, CDCl3) δ ppm 1.12 (t, J=7.5 Hz, 3H), 2.35 (s, 3H), 2.44-2.49 (m, 6H), 3.81-3.98 (m, 7H), 6.95-6.96 (m, 1H), 7.23-7.26 (m, 1H), 7.37-7.47 (m, 2H), 10.46 (s, 1H). [M+H] calc'd for C20H25N6O2, 381; found, 381.

Workup

  1. extractionthe resulting mixture was extracted with EtOAc
  2. washThe organic layers were washed with aq NaHCO3, water, and brine
  3. dry with materialwere dried over anhydrous Na2SO4
  4. filtrationfiltered through SiO2
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by column chromatography (SiO2 hexanes/EtOAc=5/1)

Sources & evidence

ORD record
ord-d36e9ba6759c47aba41ad7950651b976
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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