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 1931679노트

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HRID 1931679 반응식
[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]

참가 물질

7

반응물 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-carboxylate2회

생성물 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 ester수율 33%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
160 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-658f537052d749cbb64f42a5f0bae36f
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188098B2

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