Diethyl (ethoxymethylene)malonate → HCID 178469630, compound

HRID 1499479Notes

Reaction equation

HRID 1499479 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][N:8]2[C:12]([NH2:13])=[CH:11][CH:10]=[N:9]2)=[CH:5][CH:4]=1.C([O:18][CH:19]=[C:20]([C:26](OCC)=O)[C:21]([O:23][CH2:24][CH3:25])=[O:22])C>C1(OC2C=CC=CC=2)C=CC=CC=1>[OH:18][C:19]1[C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:26][N:13]=[C:12]2[N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:15][CH:14]=3)[N:9]=[CH:10][C:11]=12

Participants

4

Reactant 2

HCID 6871Diethyl (ethoxymethylene)malonateHCID 31612621-((4-methoxyphenyl)methyl)-1H-pyrazol-5-amine

Product 1

HCID 178469630HCID 178469630, compoundYield 122.2%

Reagents, catalysts & solvents 1

HCID 7583Diphenyl EtherSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(4-methoxybenzyl)-1H-pyrazol-5-amine (3 g, 10 mmol) and (ethoxymethylene)propanedioic acid, diethyl ester (3.8 g, 18 mmol) was heated at 120° C. for 1.5 h, then allowed to cool. After cooling, the mixture was concentrated and the resulting residue was purified with CombiFlash® eluting with 0-30% EtOAc in hexanes to give an intermediate, LCMS (M+H): 374.1. The intermediate was dissolved in diphenyl ether (5 mL). The resulted solution was heated at 240° C. in microwave reactor for 1 h 20 min. After cooling, the solid crashed out was filtered and washed with hexanes to afford 4.0 g (80%) of the sub-title compound. LCMS calc. for C17H18N3O4 (M+H)+: m/z=328.1. Found: 328.1.

Workup

  1. temperatureto cool
  2. temperatureAfter cooling
  3. concentrationthe mixture was concentrated
  4. customthe resulting residue was purified with CombiFlash®
  5. washeluting with 0-30% EtOAc in hexanes
  6. customto give an intermediate, LCMS (M+H)
  7. temperatureThe resulted solution was heated at 240° C. in microwave reactor for 1 h 20 min
  8. temperatureAfter cooling
  9. filtrationthe solid crashed out was filtered
  10. washwashed with hexanes

Sources & evidence

ORD record
ord-32d9396e766f4ff1ab1787dc61526b0f
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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