tert-Butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate → 5-Oxo-2-(4-phenoxyphenyl)-7-(piperidin-4-yl)-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 64353ノート

反応式

HRID 64353 の反応式
[NH2:1][C:2]1[NH:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:9][CH:8]=2)[C:3]=1[C:20]([NH2:22])=[O:21].C([O:25][C:26](=O)[CH2:27][C:28]([CH:30]1[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]1)=O)C>CC(O)=O>[O:25]=[C:26]1[CH:27]=[C:28]([CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[N:6]2[N:5]=[C:4]([C:7]3[CH:8]=[CH:9][C:10]([O:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)=[CH:11][CH:12]=3)[C:3]([C:20]([NH2:22])=[O:21])=[C:2]2[NH:1]1

参加物

4

反応物 2

HCID 6618868tert-Butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylateHCID 178513497HCID 178513497、化合物

生成物 1

HCID 1369280745-Oxo-2-(4-phenoxyphenyl)-7-(piperidin-4-yl)-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxamide収率 50%

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

反応条件

温度
90 °C

実験手順

A mixture of 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carboxamide (412 mg, 1.4 mmol) and tert-butyl 4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (420 mg, 1.4 mmol) in HOAc (20 mL) was stirred at 90° C. for 16 hr. The solvent was removed under vacuum, and the residue was partitioned between aq. NaHCO3 and ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by Pre-HPLC eluting from 25% to 90% CH3CN in 0.1% TFA in H2O. Fractions containing the desired product were combined and lyophilized overnight to afford 5-oxo-2-(4-phenoxyphenyl)-7-(piperidin-4-yl)-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxamide (0.3 g, 50%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.71 (br s, 1H), 8.68-8.65 (m, 1H), 8.42-8.39 (m, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.47-7.41 (m, 2H), 7.22-7.18 (m, 1H), 7.14-7.09 (m, 4H), 5.72 (s, 1H), 3.50-3.35 (m, 2H), 3.17-3.06 (m, 1H), 3.01-2.87 (m, 2H), 2.15-2.05 (m, 2H), 1.83-1.72 (m, 2H). MS (ESI) m/e [M+1]+ 430.1.

後処理

  1. customThe solvent was removed under vacuum
  2. customthe residue was partitioned between aq. NaHCO3 and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by Pre-HPLC
  7. washeluting from 25% to 90% CH3CN in 0.1% TFA in H2O
  8. additionFractions containing the desired product
  9. waitlyophilized overnight

出典と根拠

ORDレコード
ord-c6a7b0f2b34245b98ad6e3b13a3e7205
出典データセット
uspto-grants-2016_09
特許番号
US09447106B2

反応ノート

読み込み中…