Cesium hydroxide → 5-(5-Aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 1910672ノート

反応式

HRID 1910672 の反応式
Cl[C:2]1[C:3]2[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:4]=2[N:5]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[C:6](=[O:17])[CH:7]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:16])[N:8]=1.CC1(C)C(C)(C)OB([C:40]2[CH:41]=[C:42]([NH2:46])[CH:43]=[N:44][CH:45]=2)O1.[OH-].[Cs+]>O1CCOCC1.O.CCOC(C)=O.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>[NH2:46][C:42]1[CH:41]=[C:40]([C:2]2[C:3]3[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:4]=3[N:5]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[C:6](=[O:17])[CH:7]([CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:16])[N:8]=2)[CH:45]=[N:44][CH:43]=1

参加物

7

反応物 3

HCID 62750Cesium hydroxideHCID 438110685-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamineHCID 595943935,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

生成物 1

HCID 672834995-(5-Aminopyridin-3-yl)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one収率 33.4%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 8857Ethyl Acetate溶媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
90 °C

実験手順

5,7-Dichloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (240 mg) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (134 mg, 1.2 eq) were suspended in dioxane/water (6 mL/2 mL), and then cesium hydroxide (170 mg, 2 eq) was added and the mixture was degassed by pulling vacuum until bubbling occurred, and then introducing nitrogen gas. The degassing procedure was repeated twice, and then tetrakis(triphenylphosphine)palladium(0) (30 mg, 0.05 eq) was added. The degassing procedure was repeated once, and then the reaction was heated to 90° C. for three hours. The crude mixture was then diluted with EtOAc (20 mL) and then washed with water, then brine, and then it was dried over sodium sulfate, and concentrated onto silica gel. The product was purified by chromatography (gradient: 75:25 hexanes:EtOAc to EtOAc) delivering the product as a solid (90 mg, 33% yield). MS (ES+) m/z 531.0 (M+1).

後処理

  1. customthe mixture was degassed
  2. customuntil bubbling
  3. washwashed with water
  4. dry with materialbrine, and then it was dried over sodium sulfate
  5. concentrationconcentrated onto silica gel
  6. customThe product was purified by chromatography (gradient: 75:25 hexanes:EtOAc to EtOAc)

出典と根拠

ORDレコード
ord-17cd510d39ee491b9fc8a42fdd7f94d5
出典データセット
uspto-grants-2013_12
特許番号
US08604023B2

反応ノート

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