Butanedioic acid, 2-acetyl-, 1,4-diethyl ester → HCID 178470702, compound

HRID 1630303Notes

Reaction equation

HRID 1630303 reaction equation
[NH2:1][C:2]1[NH:6][N:5]=[C:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:3]=1.[C:12]([CH:15]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:16](OCC)=[O:17])(=O)[CH3:13]>CC1C=CC=CC=1C.S(O)(C1C=CC(C)=CC=1)(=O)=O.O>[CH2:25]([O:24][C:22](=[O:23])[CH2:21][C:15]1[C:12]([CH3:13])=[N:1][C:2]2[N:6]([N:5]=[C:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:3]=2)[C:16]=1[OH:17])[CH3:26]

Participants

5

Reactant 2

HCID 66197Butanedioic acid, 2-acetyl-, 1,4-diethyl esterHCID 178469278HCID 178469278, compound

Product 1

HCID 178470702HCID 178470702, compoundYield 75.3%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 7237O-XyleneSolvent

Procedure

A suspension of ethyl 5-amino-1H-pyrazole-3-carboxylate (35.5 g, 229 mmol, prepared according to WO 2008015271), diethyl 2-acetylsuccinate (51.2 mL, 275 mmol) and Ts-OH.H2O (0.218 g, 1.144 mmol) in o-xylene (500 mL) was refluxed using Dean-Stork condensor for 5 h. (Note: The suspension turned clear homogeneous solution and then in about 15 min yellow solid started crashing out of the reaction). Then, the reaction mixture was cooled, diluted with hexanes (250 mL), filtered, washed with hexanes and dried to afford ethyl 6-(2-ethoxy-2-oxoethyl)-7-hydroxy-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (53 g, 75% yield) as light yellow solid. 1H NMR (500 MHz, DMSO-d6) δ: 12.61 (br. s., 1H), 6.49 (s, 1H), 4.34 (q, J=7.1 Hz, 2H), 4.09 (q, J=7.1 Hz, 2H), 3.57 (s, 2H), 2.34 (s, 3H), 1.33 (t, J=7.2 Hz, 3H), 1.19 (t, J=7.0 Hz, 3H). LCMS (M+H)=308.04.

Workup

  1. temperaturewas refluxed
  2. customfor 5 h.
  3. customin about 15 min yellow solid started crashing out of the reaction)
  4. temperatureThen, the reaction mixture was cooled
  5. filtrationfiltered
  6. washwashed with hexanes
  7. customdried

Sources & evidence

ORD record
ord-588ed7e576534ceca6aeffd1f2fddbf6
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

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