Sodium Hydroxide → {1-[5-(1H-pyrazol-4-yl)-pyridin-2-yl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 2038758ノート

反応式

HRID 2038758 の反応式
[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15](I)=[CH:14][N:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(OC([N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1)=O)(C)(C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+]>COCCOC.O.CCO>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:30]3[CH:31]=[N:27][NH:28][CH:29]=3)=[CH:14][N:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 4

HCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 67509277Tert-butyl (1-(5-iodopyridin-2-YL)cyclobutyl)carbamate

生成物 1

HCID 68379199{1-[5-(1H-pyrazol-4-yl)-pyridin-2-yl]-cyclobutyl}-carbamic acid tert-butyl ester収率 103.4%

試薬・触媒・溶媒 1

HCID 86587095Dimethoxyethane ethanol water溶媒

反応条件

温度
100 °C

実験手順

To a mixture of [1-(5-iodo-pyridin-2-yl)-cyclobutyl]-carbamic acid tert-butyl ester (0.46 g, 1.23 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (0.4 g, 1.35 mmol), and PdCl2(dppf)Cl2.dichloromethane complex (0.2 g, 0.25 mmol) in DME/H2O/EtOH (4 mL, 7:3:2) in a sealable microwave tube was added 1M K3PO4 (1.5 mL, 1.5 mmol). The tube was sealed and heated in microwave at 100° C. for 10 minutes and then 120° C. for 20 minutes. 2M NaOH was added (2 mL) and stirred for 10 minutes. The solution was extracted with EtOAc (100 mL). The organic phase was washed with brine, dried over MgSO4, filtered through diatomaceous earth, and concentrated. The crude oil was purified via normal phase flash chromatography on silica gel eluting with 0-6% MeOH/CH2Cl2, to afford {1-[5-(1H-pyrazol-4-yl)-pyridin-2-yl]-cyclobutyl}-carbamic acid tert-butyl ester (0.40 g) as a brown solid, m/z 315.5 [M+H]+.

後処理

  1. customThe tube was sealed
  2. extractionThe solution was extracted with EtOAc (100 mL)
  3. washThe organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered through diatomaceous earth
  6. concentrationconcentrated
  7. customThe crude oil was purified via normal phase flash chromatography on silica gel eluting with 0-6% MeOH/CH2Cl2

出典と根拠

ORDレコード
ord-aa4f67022714402f8362e0d108ff037c
出典データセット
uspto-grants-2013_11
特許番号
US08575360B2

反応ノート

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