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

HRID 921065Notes

Reaction equation

HRID 921065 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.CC1C=CC(S(O)(=O)=O)=CC=1.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 TsOH.H2O (0.218 g, 1.144 mmol) in o-xylene (500 mL) was refluxed using a Dean-Stork condenser for 5 h. (Note: The suspension turned into a clear homogeneous solution and then in about 15 min a yellow solid started precipitated out of solution). 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+1)=308.04.

Workup

  1. temperaturewas refluxed
  2. customfor 5 h.
  3. customin about 15 min a yellow solid started precipitated out of solution)
  4. temperatureThen, the reaction mixture was cooled
  5. additiondiluted with hexanes (250 mL)
  6. filtrationfiltered
  7. washwashed with hexanes
  8. customdried

Sources & evidence

ORD record
ord-f2953e4e0a7e497197991f14d8aceb69
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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