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

HRID 2387739ノート

反応式

HRID 2387739 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒

反応条件

温度
140 °C

実験手順

(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).

後処理

  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)

出典と根拠

ORDレコード
ord-d9b2559dd97742eca766a3777d0d9e48
出典データセット
uspto-grants-2012_09
特許番号
US08268848B2

反応ノート

読み込み中…