Dichloromethane → 4-[4-(2-Methyl-6-[1,2,4]triazol-1-yl-pyridin-3-yloxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931706

반응식

HRID 1931706 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].[CH3:24][C:25]1[C:30](N)=[CH:29][CH:28]=[C:27]([N:32]2[CH:36]=[N:35][CH:34]=[N:33]2)[N:26]=1.C(=O)([O-])[O-:38].[K+].[K+].ClCCl>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:38][C:30]4[C:25]([CH3:24])=[N:26][C:27]([N:32]5[CH:36]=[N:35][CH:34]=[N:33]5)=[CH:28][CH:29]=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 6344DichloromethaneHCID 11430Potassium CarbonateHCID 532992722-methyl-6-(1H-1,2,4-triazol-1-yl)pyridin-3-amine2회HCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2회

생성물 1

HCID 445146854-[4-(2-Methyl-6-[1,2,4]triazol-1-yl-pyridin-3-yloxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester수율 68%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

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; 100 mg, 0.30 mmol), 2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-ol (Intermediate 7; 68 mg, 0.385 mmol), and potassium carbonate (53 mg, 0.385 mmol) in dimethylformamide (3 mL) was heated in the microwave oven at 160° C. for 10 min. Dichloromethane and water were added, and the aqueous layer was extracted three times with dichloromethane. The dichloromethane layers were combined, evaporated, and purified by preparative C18 HPLC, eluting with 10-100% acetonitrile/water. Samples containing the product were extracted three times with dichloromethane and the solvent was evaporated to give 4-[4-(2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-yloxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (96 mg, 68%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 1.95-2.04 (m, 2H), 2.20-2.35 (m, 2H), 2.90-3.05 (m, 2H), 4.25-4.40 (m, 2H), 4.90-5.02 (m, 1H), 7.69 (d, 1H, J=8.5 Hz), 7.86 (d, 1H, J=8.8 Hz), 8.12 (s, 1H), 8.17 (s, 1H), 8.47 (s, 1H), 9.20 (s, 1H). Mass spectrum (ES) MH+=478. HRMS Calcd. for C23H28N9O3 (MH+): 478.2310. Found: 478.2307.

후처리

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

출처 및 근거

ORD 기록
ord-ea5f99517cc6414fa45ca1da1ec15438
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188098B2

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