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

反応式

HRID 1931706 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].[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]

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 532992722-methyl-6-(1H-1,2,4-triazol-1-yl)pyridin-3-amine2 回HCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2 回

生成物 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 ester収率 68%

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; 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.

後処理

  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

出典と根拠

ORDレコード
ord-ea5f99517cc6414fa45ca1da1ec15438
出典データセット
uspto-grants-2012_05
特許番号
US08188098B2

関連ノート

読み込み中…