Cesium carbonate → tert-Butyl 6-(7-chloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-carboxylate

HRID 1910684ノート

反応式

HRID 1910684 の反応式
Cl[C:2]1[C:3]2[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:4]=2[N:5]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[C:6](=[O:18])[CH:7]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])[N:8]=1.[O:33]=[C:34]1[N:51](C(OC(C)(C)C)=O)[C:37]2=[N:38][CH:39]=[C:40](B3OC(C)(C)C(C)(C)O3)[CH:41]=[C:36]2[N:35]1[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60].C(=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[Li+]>O1CCOCC1.O>[Cl:32][C:30]1[CH:29]=[CH:28][C:4]2[N:5]([CH2:19][C:20]3[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=3)[C:6](=[O:18])[CH:7]([CH2:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:17])[N:8]=[C:2]([C:40]3[CH:41]=[C:36]4[N:35]([C:59]([O:61][C:62]([CH3:63])([CH3:64])[CH3:65])=[O:60])[C:34](=[O:33])[NH:51][C:37]4=[N:38][CH:39]=3)[C:3]=2[CH:31]=1

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 433294Lithium ChlorideHCID 67282666di-tert-butyl 2-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazo[4,5-b]pyridine-1,3(2H)-dicarboxylateHCID 672834205,7-Dichloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

生成物 1

HCID 67471943tert-Butyl 6-(7-chloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-carboxylate収率 26.1%

試薬・触媒・溶媒 1

HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
80 °C

実験手順

5,7-Dichloro-3-(2-chlorophenethyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (245 mg) and di-tert-butyl 2-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazo[4,5-b]pyridine-1,3(2H)-dicarboxylate (255 mg, 1.1 eq) were dissolved in dioxane/water (2 mL:0.65 mL), and cesium carbonate (327 mg, 2 eq) was added followed by lithium chloride (64 mg, 3 eq). The mixture was degassed with nitrogen and then tetrakis-triphenylphosphine palladium (0) (58 mg, 0.1 eq) was added. The mixture was degassed again, and the reaction was then heated to 80° C. for three hours. The crude mixture was partitioned between water and EtOAc and the organic fraction was then washed with brine, then dried over sodium sulfate and concentrated onto silica gel and purified by chromatography (gradient: 9:1 hexanes:EtOAc to EtOAc) delivering both the product 90 mg, 23% yield). MS (ES+) m/z 707.9 (M+Na) and m/z 807.9 (M+Na+Boc) and doubly Boc-protected material.

後処理

  1. customThe mixture was degassed with nitrogen
  2. customThe mixture was degassed again
  3. customThe crude mixture was partitioned between water and EtOAc
  4. washthe organic fraction was then washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated onto silica gel
  7. custompurified by chromatography (gradient: 9:1 hexanes:EtOAc to EtOAc)

出典と根拠

ORDレコード
ord-e11eea1f02e54f36823039e21745c3a7
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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