4-(Bromomethyl)-2,2-dimethyl-1,3-dioxolane → N-(1-((1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-5-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79280ノート

反応式

HRID 79280 の反応式
[NH:1]1[CH:5]=[CH:4][C:3]([CH2:6][N:7]2[C:15]3[C:10](=[C:11]([NH:16][C:17]([C:19]4[N:23]5[CH:24]=[CH:25][CH:26]=[CH:27][C:22]5=[N:21][CH:20]=4)=[O:18])[CH:12]=[CH:13][CH:14]=3)[C:9]([CH2:28][CH3:29])=[N:8]2)=[N:2]1.Br[CH2:31][CH:32]1[CH2:36][O:35][C:34]([CH3:38])([CH3:37])[O:33]1.O.[OH-].[Cs+]>CN(C)C=O>[CH3:37][C:34]1([CH3:38])[O:33][CH:32]([CH2:31][N:2]2[C:3]([CH2:6][N:7]3[C:15]4[C:10](=[C:11]([NH:16][C:17]([C:19]5[N:23]6[CH:24]=[CH:25][CH:26]=[CH:27][C:22]6=[N:21][CH:20]=5)=[O:18])[CH:12]=[CH:13][CH:14]=4)[C:9]([CH2:28][CH3:29])=[N:8]3)=[CH:4][CH:5]=[N:1]2)[CH2:36][O:35]1

参加物

5

反応物 3

HCID 1697594-(Bromomethyl)-2,2-dimethyl-1,3-dioxolaneHCID 23679066Caesium hydroxide--water (1/1/1)HCID 178437952HCID 178437952、化合物

生成物 1

HCID 67260734N-(1-((1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-5-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of N-(1-((1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (40 mg, 0.104 mmol) in N,N-dimethylformamide (0.5 mL) was added 4-(bromomethyl)-2,2-dimethyl-1,3-dioxolane (20.2 mg, 0.104 mmol) and cesium hydroxide hydrate (17.4 mg, 0.104 mmol). The mixture was stirred for 16 hours at ambient temperature, filtered, washing with methanol and ethyl acetate, and concentrated under a stream of nitrogen. The resulting material was purified using preparative thin layer chromatography on silica, eluting with 10% methanol in dichloromethane. The isolated product (22.5 mg) was a 7:3 mixture of two regioisomers, N-(1-((1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-5-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(1-((1-(2,3-dihydroxypropyl)-1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide. This material was continued to the next step as a mixture.

後処理

  1. filtrationfiltered
  2. washwashing with methanol and ethyl acetate
  3. concentrationconcentrated under a stream of nitrogen
  4. customThe resulting material was purified
  5. washeluting with 10% methanol in dichloromethane
  6. additiona 7:3 mixture of two regioisomers, N-(1-((1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-5-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(1-((1-(2,3-dihydroxypropyl)-1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

出典と根拠

ORDレコード
ord-bca7df72b6594554ae61604e328be30f
出典データセット
uspto-grants-2014_09
特許番号
US08841455B2

反応ノート

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