Ethyl Acetate → HCID 59785001, compound

HRID 470324Notes

Reaction equation

HRID 470324 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[CH2:8][CH2:7][C:6]3[CH:12]=[C:13]([O:16][CH3:17])[CH:14]=[CH:15][C:5]=3[C:4]=2[N:3]=1.[CH2:18]([O:20][C:21]([C:23]1[C:24]([NH2:28])=[N:25][NH:26][CH:27]=1)=[O:22])[CH3:19].C([O-])([O-])=O.[Cs+].[Cs+].CCOC(C)=O>CN(C=O)C.O>[CH2:18]([O:20][C:21]([C:23]1[C:24]([NH2:28])=[N:25][N:26]([C:2]2[N:11]=[CH:10][C:9]3[CH2:8][CH2:7][C:6]4[CH:12]=[C:13]([O:16][CH3:17])[CH:14]=[CH:15][C:5]=4[C:4]=3[N:3]=2)[CH:27]=1)=[O:22])[CH3:19]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 53486023HCID 53486023, compoundHCID 178469928HCID 178469928, compound

Product 1

HCID 59785001HCID 59785001, compoundYield 54.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-Chloro-8-methoxy-5,6-dihydro-benzo[h]quinazoline (2, 5.0 g, 20.27 mM), 3-Amino-1H-pyrazole-4-carboxylic acid ethyl ester (3.14 g, 20.27 mM), Cs2CO3 (8.59 g, 26.35 mM) in DMF (40 ml) was stirred at 100° C. for 2.5 hr then cooled to room temperature and diluted with water (400 ml). The resulting precipitate was isolated via filtration and the solid washed with water (3×50 mL) then methanol (3×30 ml). The solid was dried under reduced pressure which was comprised of a 7:3 mixture of 3-Amino-1-(8-methoxy-5,6-dihydro-benzo[h]quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester(3) and it's isomer 5-Amino-1-(5,6-dihydro-benzo[h]quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester identical to the material prepared in preparation 6 below. The solid was then crystallized from dichloromethane (40 ml) to give the slower (TLC, EtOAc) of two isomers 3-Amino-1-(8-methoxy-5,6-dihydro-benzo[h]quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester (3, 4.0 g, 2 crops, 54% yield). ES-MS MH+ 366. The mother liquors may be purified via chromatography on silica eluting with ethyl acetate to provide the faster isomer 5-Amino-1-(5,6-dihydro-benzo[h]quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester.

Workup

  1. temperaturethen cooled to room temperature
  2. customThe resulting precipitate was isolated via filtration
  3. washthe solid washed with water (3×50 mL)
  4. customThe solid was dried under reduced pressure which
  5. additionwas comprised of a 7:3 mixture of 3-Amino-1-(8-methoxy-5,6-dihydro-benzo[h]quinazolin-2-yl)-1H-pyrazole-4-carboxylic acid ethyl ester(3)
  6. customprepared in preparation 6 below
  7. customThe solid was then crystallized from dichloromethane (40 ml)

Sources & evidence

ORD record
ord-97a89575a1524a3fa3d4d742b836d00e
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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