Cesium carbonate → 3-{1-[5-(3,4-Dimethyl-2-oxo-2,3-dihydro-benzoxazole-6-carbonyl)-2-fluoro-phenyl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

HRID 469432ノート

反応式

HRID 469432 の反応式
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]2[NH:7][C:8](=[O:18])[N:9]([CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:10][CH2:11][C:5]=2[CH:4]=1.Br[C:22]1[CH:23]=[C:24]([CH:39]=[CH:40][C:41]=1[F:42])[C:25]([C:27]1[CH:37]=[C:36]([CH3:38])[C:30]2[N:31]([CH3:35])[C:32](=[O:34])[O:33][C:29]=2[CH:28]=1)=[O:26].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:35][N:31]1[C:30]2[C:36]([CH3:38])=[CH:37][C:27]([C:25]([C:24]3[CH:23]=[CH:22][C:41]([F:42])=[C:40]([N:15]4[CH2:14][CH2:13][CH:12]([N:9]5[CH2:10][CH2:11][C:5]6[CH:4]=[C:3]([O:2][CH3:1])[CH:20]=[CH:19][C:6]=6[NH:7][C:8]5=[O:18])[CH2:17][CH2:16]4)[CH:39]=3)=[O:26])=[CH:28][C:29]=2[O:33][C:32]1=[O:34]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 183568527-methoxy-3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 581811086-(3-bromo-4-fluoro-benzoyl)-3,4-dimethyl-3H-benzoxazol-2-one

生成物 1

HCID 252669643-{1-[5-(3,4-Dimethyl-2-oxo-2,3-dihydro-benzoxazole-6-carbonyl)-2-fluoro-phenyl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

Under an argon atmosphere 330 mg (1.20 mmol) 7-methoxy-3-piperidin-4-yl-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one, 437 mg (1.20 mmol) 6-(3-bromo-4-fluoro-benzoyl)-3,4-dimethyl-3H-benzoxazol-2-one and 586 mg (1.80 mmol) caesium carbonate were combined in 10 mL dioxane, then mixed with 75 mg (0.12 mmol) BINAP and 27 mg (0.12 mmol) palladium(II)acetate and stirred for 48 h at 100° C. The mixture was evaporated down, the residue was dissolved in DMF/MeOH and purified by preparative HPLC-MS. The fractions containing the product were combined and the acetonitrile was evaporated down. The aqueous residue was made basic with 1N aqueous sodium hydroxide solution, the precipitate formed was suction filtered and washed with water and dried. As the product was still contaminated, it was then purified again by preparative HPLC-MS.

後処理

  1. customThe mixture was evaporated down
  2. dissolutionthe residue was dissolved in DMF/MeOH
  3. custompurified by preparative HPLC-MS
  4. additionThe fractions containing the product
  5. customthe acetonitrile was evaporated down
  6. customthe precipitate formed
  7. filtrationfiltered
  8. washwashed with water
  9. customdried
  10. customit was then purified again by preparative HPLC-MS

出典と根拠

ORDレコード
ord-457fe07086c44c06a8790501ce4bab55
出典データセット
uspto-grants-2014_01
特許番号
US08629137B2

反応ノート

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