Ethyl Acetate → 4-[4-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931679ノート

反応式

HRID 1931679 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22](Cl)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:24]1[C:28]2=[N:29][CH:30]=[C:31]([OH:33])[CH:32]=[C:27]2[CH:26]=[CH:25]1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([O:33][C:31]4[CH:32]=[C:27]5[CH:26]=[CH:25][NH:24][C:28]5=[N:29][CH:30]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 220307221H-Pyrrolo[2,3-b]pyridin-5-olHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2 回

生成物 1

HCID 579650464-[4-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester収率 33%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
160 °C

実験手順

A mixture of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 50 mg, 0.15 mmol), 1H-pyrrolo[2,3-B]pyridin-5-ol (Matrix Scientific, Columbia, S.C., USA; 26 mg, 0.19 mmol), and potassium carbonate (27 mg, 0.19 mmol) in dimethylformamide (2 mL) was heated in the microwave oven at 160° C. for 10 min. Ethyl acetate and water were added, and the aqueous layer was extracted twice with ethyl acetate. The ethyl acetate layers were combined, evaporated, and purified by preparative C18 HPLC, eluting with 10-100% acetonitrile/water. Samples containing the product were extracted twice with dichloromethane and the solvent was evaporated under high vacuum to give 4-[4-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (21 mg, 33%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ 1.43 (s, 9H), 1.80-2.15 (m, 4H), 3.02 (br s, 2H), 4.08 (d, 2H, J=12.4 Hz), 4.85-5.10 (m, 1H), 6.45-6.52 (m, 1H), 7.58 (d, 1H, J=2.9 Hz), 7.94 (d, 1H, J=2.5 Hz), 8.20 (d, 1H, J=2.5 Hz), 8.22 (s, 1H), 8.50 (s, 1H), 11.85 (br s, 1H). Mass spectrum (ES) MH+=436. HRMS Calcd. for C22H26N7O3 (MH+): 436.2092. Found: 436.2090.

後処理

  1. extractionthe aqueous layer was extracted twice with ethyl acetate
  2. customevaporated
  3. custompurified by preparative C18 HPLC
  4. washeluting with 10-100% acetonitrile/water
  5. additionSamples containing the product
  6. extractionwere extracted twice with dichloromethane
  7. customthe solvent was evaporated under high vacuum

出典と根拠

ORDレコード
ord-658f537052d749cbb64f42a5f0bae36f
出典データセット
uspto-grants-2012_05
特許番号
US08188098B2

反応ノート

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