Sodium Bicarbonate → HCID 178480956、化合物

HRID 897503ノート

反応式

HRID 897503 の反応式
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[C:35]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH:36]=[CH:37][CH:38]=2)O1.O.C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>O.COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:33]3[CH:34]=[C:35]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:44])([CH3:43])[CH3:45])[CH:36]=[CH:37][CH:38]=3)[C:10]=12

参加物

8

反応物 4

HCID 516892Sodium BicarbonateHCID 2735133Sodium Carbonate MonohydrateHCID 2773617tert-Butyl [3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamateHCID 178481014HCID 178481014、化合物

生成物 1

HCID 178480956HCID 178480956、化合物収率 81.1%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

A mixture of cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1.89 g, 4.28 mmol, 1 equiv), tert-butyl N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (1.64 g, 5.14 mmol, 1.2 equiv), tetrakis(triphenylphosphine)palladium (0.271 g, 0.257 mmol, 0.06 equiv), and sodium carbonate monohydrate (1.28 g, 10.3 mmol, 2.4 equiv) in water (13 mL) and DME (18 mL) was heated at 85° C. for 14 h. The mixture was allowed to cool to ambient temperature. Saturated aqueous sodium bicarbonate solution (15 mL) was added and the aqueous portion was extracted with EtOAc (30 mL). The organic extract was dried over MgSO4, filtered, and concentrated to afford a pale yellow solid. Purification by column chromatography on silica gel (elution with 2 L of 95:4:1 CH2Cl2:Et3N:MeOH) afforded cis-tert-butyl N-(3-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)carbamate as a white solid (1.76 g, 3.47 mmol):

後処理

  1. temperatureto cool to ambient temperature
  2. extractionthe aqueous portion was extracted with EtOAc (30 mL)
  3. extractionThe organic extract
  4. dry with materialwas dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a pale yellow solid
  8. customPurification by column chromatography on silica gel (elution with 2 L of 95:4:1 CH2Cl2:Et3N:MeOH)

出典と根拠

ORDレコード
ord-5ae7815e34604b1793da03251459dba2
出典データセット
uspto-grants-2005_07
特許番号
US06921763B2

反応ノート

読み込み中…