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Potassium Carbonate → (S)-3-{4-[2-(4-Hydroxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl ester

HRID 2272833
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HRID 2272833 반응식
Br[C:2]1[N:28]=[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][O:11][C:12]3[CH:17]=[CH:16][C:15]([C@@H:18]([C:25]#[C:26][CH3:27])[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:14][CH:13]=3)=[CH:9][N:4]2[N:3]=1.[OH:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:23]([O:22][C:20](=[O:21])[CH2:19][C@@H:18]([C:15]1[CH:16]=[CH:17][C:12]([O:11][CH2:10][C:8]2[CH:7]=[CH:6][C:5]3[N:4]([N:3]=[C:2]([C:33]4[CH:34]=[CH:35][C:30]([OH:29])=[CH:31][CH:32]=4)[N:28]=3)[CH:9]=2)=[CH:13][CH:14]=1)[C:25]#[C:26][CH3:27])[CH3:24]
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참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 118151365Ethyl (3S)-3-[4-[(2-bromo-[1,2,4]triazolo[1,5-a]pyridin-6-yl)methoxy]phenyl]hex-4-ynoate

생성물 1

HCID 136992561(S)-3-{4-[2-(4-Hydroxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl ester수율 74.8%

시약·촉매·용매 2

HCID 178418476
HCID 178418476, 화합물
촉매
HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To a stirred solution of ethyl (3S)-3-[4-[(2-bromo-[1,2,4]triazolo[1,5-a]pyridin-6-yl)methoxy]phenyl]hex-4-ynoate (1.0 g, 2.2 mmol) and 4-hydroxy phenyl boronic acid (0.37 g, 2.7 mmol) in 1,4-dioxane (30 mL) is added K2CO3 (0.91 g, 6.6 mmol). The mixture purged with nitrogen for 10 minutes. Pd(PPh3)2Cl2 (0.14 g, 0.2 mmol) is added and the mixture is heated at 100° C. for 12 hours. The reaction mixture is cooled to room temperature, filtered through diatomaceous earth, and washed with EtOAc (2×10 mL). The filtrate is dried over anhydrous sodium sulphate, filtered, and concentrated to dryness. The crude material is purified by silica gel chromatography (combiflash using 24 g redisep column) eluting with 15-20% EtOAc/hexane to give the title compound (0.75 g, 73.52%). LCMS m/z 456.2 (M+H)+.

후처리

  1. customThe mixture purged with nitrogen for 10 minutes
  2. temperatureThe reaction mixture is cooled to room temperature
  3. filtrationfiltered through diatomaceous earth
  4. washwashed with EtOAc (2×10 mL)
  5. dry with materialThe filtrate is dried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude material is purified by silica gel chromatography (combiflash using 24 g redisep column)
  9. washeluting with 15-20% EtOAc/hexane

출처 및 근거

ORD 기록
ord-134f38ec89bd4b20b5c1687b2cfd9bd1
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09120793B2

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