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Picolinic acid → Diethyl 2-(3-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)malonate

HRID 1775063
ノート
印刷プレビュー

反応式

HRID 1775063 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]3[C:28]4[C:23](=[CH:24][N:25]=[C:26](Br)[CH:27]=4)[N:22]([CH:30]4[CH2:35][CH2:34][CH2:33][CH2:32][O:31]4)[N:21]=3)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:36]([O:42][CH2:43][CH3:44])(=[O:41])[CH2:37][C:38]([O-:40])=[O:39].C(=O)([O-])[O-].[Cs+].[Cs+].N1C=CC=[CH:53][C:52]=1C(O)=O>O1CCOCC1.[Cu]I>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[C:16]([C:20]3[C:28]4[C:23](=[CH:24][N:25]=[C:26]([CH:37]([C:38]([O:40][CH2:52][CH3:53])=[O:39])[C:36]([O:42][CH2:43][CH3:44])=[O:41])[CH:27]=4)[N:22]([CH:30]4[CH2:35][CH2:34][CH2:33][CH2:32][O:31]4)[N:21]=3)[CH:17]=[CH:18][CH:19]=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

7

反応物 4

HCID 1018Picolinic acidHCID 10796Cesium carbonateHCID 3595298Propanedioic acid, monoethyl esterHCID 866766914-{6-[5-bromo-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl]-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 71253905Diethyl 2-(3-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)malonate
収率 47%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of 218 mg (0.40 mmol) of 4-{6-[5-Bromo-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl]-pyridin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester, 1.22 mL (8.02 mmol) of Ethyl malonate, 76 mg (0.40 mmol) of copper(I) iodide, 654 mg (2.006 mmol) of cesium carbonate and 99 mg (0.80 mmol) of picolinic acid in 4.0 ml of 1,4-dioxane was degassed and then heated for 24 hours at 100° C. The mixture was filtered and the filtrate concentrated in vacuum. The residue was partitioned between ethyl acetate and water, the organic extracts were washed consequently with saturated aqueous NaHCO3, 5% aqueous citric acid, water, brine, dried over MgSO4 and concentrated. The residue was purified via silica gel chromatography using a gradient of ethyl acetate in heptane to afford 117 mg (47%) of Diethyl 2-(3-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)malonate. ESI MS m/z 623.3 (M+1).

後処理

  1. customwas degassed
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate concentrated in vacuum
  4. customThe residue was partitioned between ethyl acetate and water
  5. washthe organic extracts were washed consequently with saturated aqueous NaHCO3, 5% aqueous citric acid, water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified via silica gel chromatography

出典と根拠

ORDレコード
ord-e6fcd5686e344782b651a3383c889695
出典データセット
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09260425B2

反応ノート

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