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1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 8-(2-Chloro-4-fluorophenyl)-N-(1-(6-methylpyrimidin-4-yl)piperidin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 451455
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HRID 451455 반응식
Cl.Cl.[CH3:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([N:10]2[CH2:15][CH2:14][CH:13]([NH2:16])[CH2:12][CH2:11]2)[CH:5]=1.Br[C:18]1[N:34]=[C:21]2[C:22]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=3[Cl:33])=[CH:23][CH:24]=[CH:25][N:20]2[N:19]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[O-]C1C=CC=CC=1.[Na+]>ClCCl.O1CCOCC1>[Cl:33][C:27]1[CH:28]=[C:29]([F:32])[CH:30]=[CH:31][C:26]=1[C:22]1[C:21]2[N:20]([N:19]=[C:18]([NH:16][CH:13]3[CH2:14][CH2:15][N:10]([C:6]4[CH:5]=[C:4]([CH3:3])[N:9]=[CH:8][N:7]=4)[CH2:11][CH2:12]3)[N:34]=2)[CH:25]=[CH:24][CH:23]=1
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참가 물질

7

반응물 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 4445035Phenolate SodiumHCID 673364492-Bromo-8-(2-chloro-4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridineHCID 673421331-(6-Methylpyrimidin-4-yl)piperidin-4-amine dihydrochloride

생성물 1

HCID 533537188-(2-Chloro-4-fluorophenyl)-N-(1-(6-methylpyrimidin-4-yl)piperidin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine
수율 44.3%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

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온도
130 °C

실험 절차

1-(6-Methylpyrimidin-4-yl)piperidin-4-amine dihydrochloride (133 mg, 0.5 mmol) was suspended in dichloromethane (15 mL) and then extracted with aqueous sodium hydroxide (2 M, 10 mL). The aqueous layer was extracted with dichloromethane (15 mL) and the organic layers were combined, dried over sodium sulfate and evaporated carefully. After addition of 2-bromo-8-(2-chloro-4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (180 mg, 0.55 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (23.1 mg, 0.04 mmol), tris(dibenzylideneacetone)dipalladium(o) chloroform adduct (21 mg, 0.02 mmol) and sodium phenoxide (87 mg, 0.75 mmol) in dry 1,4-dioxane (4 mL) the reaction mixture was stirred under an argon atmosphere for 60 minutes at 130° C. in the microwave. Concentration and purification of the residue by chromatography (SiO2, heptane:ethyl acetate 3:1 to 0:1) afforded the title compound as yellow foam (97 mg, 44%).

후처리

  1. extractionextracted with aqueous sodium hydroxide (2 M, 10 mL)
  2. extractionThe aqueous layer was extracted with dichloromethane (15 mL)
  3. dry with materialdried over sodium sulfate
  4. customevaporated carefully
  5. concentrationConcentration and purification of the residue by chromatography (SiO2, heptane:ethyl acetate 3:1 to 0:1)

출처 및 근거

ORD 기록
ord-dad9f949b52d456f8bc8466615647673
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08486967B2

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