تفاعل #77551

معادلة التفاعل

isobutyraldehyde

2,3-dichlorobenzaldehyde

t-butylacetoacetate

t-butoxyacetoacetate

3-aminopyrazole

sodium acetate

→

title compound

المردود 41.7%

4,7-Dihydro-5-methyl-7-(1-methylethyl)pyrazolo[1,5-a]pyrimidine-6-carboxylic acid 1,1-dimethylethyl ester

المردود 41.7%

المذيبات

dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   أخرىA pressure tube was dried with a heat gun under nitrogen
2. 2
   أخرىThe mixture was flushed with nitrogen
3. 3
   أخرىThe tube was sealed
4. 4
   درجة الحرارةThe mixture was cooled to room temperature
5. 5
   workup.ADDITIONdiluted with ethyl acetate to a volume of 20 mL
6. 6
   غسيلwashed with lithium chloride (2.4M, 10 mL) and brine
7. 7
   تجفيفdried over anhydrous sodium sulfate
8. 8
   ترشيحfiltered
9. 9
   تركيزconcentrated
10. 10
    أخرىto give 1.02 of a yellow oil
11. 11
    أخرىThe oil was purified by flash chromatography (silica, 45% ethyl acetate/heptane)

الإجراء التجريبي

A pressure tube was dried with a heat gun under nitrogen. The pressure tube was charged in the following order with isobutyraldehyde 2(0.262 g, 3.63 mmol), dimethylformamide (3 mL), t-butylacetoacetate 1 (0.574 g, 3.63 mmol), 3-aminopyrazole 3 (0.362 g, 4.36 mmol) and sodium acetate (1.22 g, 14.5 mmol). The mixture was flushed with nitrogen. The tube was sealed and warmed to 75° C. and stirred overnight. The mixture was cooled to room temperature, diluted with ethyl acetate to a volume of 20 mL, washed with lithium chloride (2.4M, 10 mL) and brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 1.02 of a yellow oil. The oil was purified by flash chromatography (silica, 45% ethyl acetate/heptane) to give 0.42 g (41% yield) of the title compound. Reverse Phase HPLC: YMC S5 ODS 4.6×50 mm Ballistic column, UV detection at 220λ, 4 min. gradient 0-100% Solvent B/A (Solvent A: 10% MeOH/H2O with 0.2% PPA, Solvent B: 90% MeOH/H2O with 0.2% PPA), 4 mL/min. Rt=3.83 min, (100% pure). Reverse Phase LC/MS: YMC S5 ODS 4.6×50 mm Ballistic column, UV detection at 220λ, 4 min. gradient 0-100% Solvent B/A (Solvent A: 10% MeOH/H2O with 0.1% TFA, Solvent B: 90% MeOH/H2O with 0.1% TFA), 4 mL/min. Rt=3.06 min. MS (EM, M+1: 278). HMR (CDCl3, 400 MHz): 7.37(1H,d,J=2.2 Hz), 6.35(1H,s), 5.55(1H,d,J=1.8 Hz), 5.29(1H,d,J=2.2 Hz), 2.41(3H,s), 1.50(9H,s), 1.28-1.19(1H,m), 1.07(3H,d,J=7.0 Hz), 0.60(3H,d,J=7.0 Hz).

المصدر