Dichloromethane → [3-Methyl-4-(2-oxo-4-pyridin-2-yl-1,2,4,5-tetrahydroimidazo[1,5,4-de][1, 4]benzoxazin-7-yl)isoxazol-5-yl]methyl benzoate

HRID 589100ノート

反応式

HRID 589100 の反応式
Br[C:2]1[C:11]2[O:10][CH2:9][CH:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[N:7]3[C:18](=[O:20])[NH:19][C:5]([C:6]=23)=[CH:4][CH:3]=1.[C:21]([O:29][CH2:30][C:31]1[O:35][N:34]=[C:33]([CH3:36])[C:32]=1B(O)O)(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.ClCCl>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:21]([O:29][CH2:30][C:31]1[O:35][N:34]=[C:33]([CH3:36])[C:32]=1[C:2]1[C:11]2[O:10][CH2:9][CH:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[N:7]3[C:18](=[O:20])[NH:19][C:5]([C:6]=23)=[CH:4][CH:3]=1)(=[O:28])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

参加物

7

反応物 3

HCID 6344Dichloromethane2 回HCID 904091467-Bromo-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-oneHCID 90409449{5-[(Benzoyloxy)methyl]-3-methylisoxazol-4-yl}boronic acid2 回

生成物 1

HCID 90409759[3-Methyl-4-(2-oxo-4-pyridin-2-yl-1,2,4,5-tetrahydroimidazo[1,5,4-de][1, 4]benzoxazin-7-yl)isoxazol-5-yl]methyl benzoate収率 60.7%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

A solution of 7-bromo-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one (687 mg, 2.07 mmol) and {5-[(benzoyloxy)methyl]-3-methylisoxazol-4-yl}boronic acid (1.08 g, 4.14 mmol) in 1,4-dioxane (15.7 mL) and water (4 mL) was degassed with nitrogen. The reaction mixture was treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (253 mg, 0.310 mmol), degassed with nitrogen, and heated in a sealed tube at 80° C. for 30 min, at which time the reaction mixture was treated with {5-[(benzoyloxy)methyl]-3-methylisoxazol-4-yl}boronic acid (1.08 g, 4.14 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (1:1) (10 mg, 12.2 mol), degassed with nitrogen and heated at 80° C. for a further 30 min. The reaction mixture was then diluted with ethyl acetate and water. The organic layer was separated and washed with brine, dried over magnesium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (30% ethyl acetate/hexanes to 100% ethyl acetate [the ethyl acetate contained 5% methanol]) gave the desired product (0.589 g, 58%) as a racemic mixture. LCMS calculated for C26H21N4O5 (M+H)+: m/z=469.1. found: 469.1.

後処理

  1. customdegassed with nitrogen
  2. customdegassed with nitrogen
  3. temperatureheated at 80° C. for a further 30 min
  4. additionThe reaction mixture was then diluted with ethyl acetate and water
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude product
  11. customPurification by flash column chromatography (30% ethyl acetate/hexanes to 100% ethyl acetate [the ethyl acetate

出典と根拠

ORDレコード
ord-509c558cb8f94cb19b9de8010e03b715
出典データセット
uspto-grants-2016_01
特許番号
US09227985B2

反応ノート

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