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Ethyl Acetate → 4-[4-(6-Methanesulfonyl-2-methyl-pyridin-3-ylamino)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931616
ノート
印刷プレビュー

反応式

HRID 1931616 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][S:25]([C:28]1[N:33]=[C:32]([CH3:34])[C:31]([NH2:35])=[CH:30][CH:29]=1)(=[O:27])=[O:26].CC(C)([O-])C.[Na+].C(OCC)(=O)C>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C.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]([NH:35][C:31]4[C:32]([CH3:34])=[N:33][C:28]([S:25]([CH3:24])(=[O:27])=[O:26])=[CH: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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

HCID 8857Ethyl AcetateHCID 23676156Sodium t-butoxideHCID 510505272-Methyl-6-(methylsulfonyl)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 579650384-[4-(6-Methanesulfonyl-2-methyl-pyridin-3-ylamino)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester
収率 46.5%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane触媒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), 6-methanesulfonyl-2-methyl-pyridin-3-ylamine (Intermediate 4; 28 mg, 0.15 mmol), palladium acetate (0.33 mg, 0.01 equivalent), sodium tert-butoxide (34 mg, 0.36 mmol), and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (Aldrich, 1 mg, 0.02 equivalents) 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 three times 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-(6-methanesulfonyl-2-methyl-pyridin-3-ylamino)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (34 mg, 46%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ 1.41 (s, 9H), 1.92-2.00 (m, 4H), 2.55 (s, 3H), 2.90-3.04 (m, 2H), 3.30 (water peak and SO2CH3 peak), 4.00-4.12 (m, 2H), 4.84-4.96 (m, 1H), 7.92 (d, 1H, J=8.5 Hz), 8.22-8.36 (m, 3H), 10.06 (br s, 1H). HRMS Calcd. for C22H30N7O4S (MH+): 488.2075. Found: 488.2073.

後処理

  1. extractionthe aqueous layer was extracted three times 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-8c91bf875d8d41d19b36e180939ab61e
出典データセット
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08188098B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート