Tetrahydrofuran → 2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)-2-{[(2-hydroxymethyl-4-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide

HRID 2387739노트

반응식

HRID 2387739 반응식
[Si]([O:8][CH2:9][Sn](CCCC)(CCCC)CCCC)(C(C)(C)C)(C)C.[CH3:23][N:24]1[CH2:28][CH2:27][CH2:26][C:25]1=O.ClC1N=C(C)C(OC[C:40]2([C:50]([NH:52][C:53]3[CH:58]=[CH:57][C:56]([F:59])=[CH:55][N:54]=3)=[O:51])[CH2:42][CH:41]2[C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([F:49])[CH:44]=2)=CN=1.[F-].C([N+:65](CCCC)(CCCC)CCCC)CCC.C1[CH2:82][O:81]CC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:49][C:45]1[CH:44]=[C:43]([C:41]2([CH2:82][O:81][C:27]3[C:26]([CH3:25])=[N:65][C:23]([CH2:9][OH:8])=[N:24][CH:28]=3)[CH2:42][CH:40]2[C:50]([NH:52][C:53]2[CH:58]=[CH:57][C:56]([F:59])=[CH:55][N:54]=2)=[O:51])[CH:48]=[CH:47][CH:46]=1

참가 물질

8

반응물 5

HCID 8028TetrahydrofuranHCID 13387N-methyl-2-pyrrolidoneHCID 2724141Tetrabutylammonium FluorideHCID 14270862Tert-butyl-dimethyl-(tributylstannylmethoxy)silaneHCID 86664273([(2-chloro-4-methylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide

생성물 1

HCID 764691762-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)-2-{[(2-hydroxymethyl-4-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매

반응 조건

온도
140 °C

실험 절차

(Tert-butyldimethylsilyloxymethyl)tri-n-butyltin (Tetrahedron Vol. 45, No. 4, 993-1006: 121 mg) and tetrakistriphenylphosphinepalladium (13.4 mg) were added to a N-methylpyrrolidone (2.5 ml) solution of the compound 323-4 (100 mg), and the obtained mixture was stirred at 140° C. for 6 hours. The temperature of the reaction solution was returned to room temperature. Thereafter, THF (2 ml) and tetrabutyl ammonium fluoride (1 M THF solution: 232 ul) were added to the reaction solution, and the obtained mixture was stirred at room temperature for 14 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride aqueous solution, dried over magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-heptane:ethyl acetate=19:1 to 1:1), so as to obtain the title compound (26.6 mg).

후처리

  1. customwas returned to room temperature
  2. stirringthe obtained mixture was stirred at room temperature for 14 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe obtained organic layer was washed with a saturated sodium chloride aqueous solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (n-heptane:ethyl acetate=19:1 to 1:1)

출처 및 근거

ORD 기록
ord-d9b2559dd97742eca766a3777d0d9e48
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08268848B2

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