Methyl 4-cyano-2-(4-ethylpiperazin-1-yl)-6-(m-tolylamino)pyrimidine-5-carboxylate → 2-(4-Ethylpiperazin-1-yl)-4-(m-tolylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-one

HRID 515968Notes

Reaction equation

HRID 515968 reaction equation
[C:1]([C:3]1[C:8]([C:9]([O:11]C)=O)=[C:7]([NH:13][C:14]2[CH:15]=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=2)[N:6]=[C:5]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH3:28])[CH2:23][CH2:22]2)[N:4]=1)#[N:2]>[Pd].CCO.Cl>[CH2:27]([N:24]1[CH2:23][CH2:22][N:21]([C:5]2[N:6]=[C:7]([NH:13][C:14]3[CH:15]=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=3)[C:8]3[C:9](=[O:11])[NH:2][CH2:1][C:3]=3[N:4]=2)[CH2:26][CH2:25]1)[CH3:28]

Participants

5

Reactant 1

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

Product 1

HCID 532519482-(4-Ethylpiperazin-1-yl)-4-(m-tolylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-5-oneYield 43%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Procedure

A mixture of methyl 4-cyano-2-(4-ethylpiperazin-1-yl)-6-(m-tolylamino)pyrimidine-5-carboxylate (49.8 mg, 0.131 mmol) and palladium on carbon (10.1 mg) in EtOH (3 mL) and 1N HCl (3 mL) was stirred at RT for 2 h under a hydrogen atmosphere. The insoluble materials were filtered off, and the filtrate was concentrated under reduced pressure. The residue was treated with saturated aq NaHCO3 and EtOAc for 3 h. The mixture was extracted with EtOAc. The organic layers were washed with aq NaHCO3, water, and brine, were dried over anhydrous Na2SO4, and then filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography twice (SiO2, EtOAc then DM1020 EtOAc/MeOH=20/1) to give the title compound as a white solid (19.8 mg, 43%). 1H NMR (500 MHz, CDCl3) δ ppm 1.19 (br s, 3H), 2.36 (s, 3H), 2.5 (br s, 6H), 4.08 (br s, 4H), 4.23 (s, 2H), 5.50 (s, 1H), 6.91-6.92 (m, 1H), 7.22-7.26 (m, 1H), 7.49-7.54 (m, 2H), 8.44 (s, 1H). [M+H] calc'd for C19H25N6O, 353; found, 353.

Workup

  1. filtrationThe insoluble materials were filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. additionThe residue was treated with saturated aq NaHCO3 and EtOAc for 3 h
  4. extractionThe mixture was extracted with EtOAc
  5. washThe organic layers were washed with aq NaHCO3, water, and brine
  6. dry with materialwere dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by column chromatography twice (SiO2, EtOAc

Sources & evidence

ORD record
ord-3690a656a3704095a4256755d063d38a
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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