Isobutyl chloroformate → 1,1-dimethylethyl 7-(2-[(2-fluoroethyl)amino]-1-{[(2-methylpropyl)oxy]carbonyl}-1H-benzimidazol-5-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 473881ノート

反応式

HRID 473881 の反応式
Br[C:2]1[CH:21]=[CH:20][C:5]2[N:6]([C:13]([O:15][CH2:16][CH:17]([CH3:19])[CH3:18])=[O:14])[C:7]([NH:9][CH2:10][CH2:11][F:12])=[N:8][C:4]=2[CH:3]=1.[CH3:22][C:23]([O:26][C:27]([N:29]1[CH2:35][C:34]2[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][C:33]=2[O:32][CH2:31][CH2:30]1)=[O:28])([CH3:25])[CH3:24].CCN(C(C)C)C(C)C.ClC(OCC(C)C)=O>C(OCC)(=O)C.O.O1CCOCC1>[F:12][CH2:11][CH2:10][NH:9][C:7]1[N:6]([C:13]([O:15][CH2:16][CH:17]([CH3:19])[CH3:18])=[O:14])[C:5]2[CH:20]=[CH:21][C:2]([C:37]3[CH:38]=[CH:39][C:33]4[O:32][CH2:31][CH2:30][N:29]([C:27]([O:26][C:23]([CH3:24])([CH3:22])[CH3:25])=[O:28])[CH2:35][C:34]=4[CH:36]=3)=[CH:3][C:4]=2[N:8]=1

参加物

8

反応物 4

HCID 62365Isobutyl chloroformateHCID 81531Diisopropylethylamine2 回HCID 59604707(4-(Tert-butoxycarbonyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepin-7-yl)boronic acidHCID 86647855Isobutyl 5-bromo-2-(2-fluoroethylamino)-1H-benzo[d]imidazole-1-carboxylate

生成物 1

HCID 866720291,1-dimethylethyl 7-(2-[(2-fluoroethyl)amino]-1-{[(2-methylpropyl)oxy]carbonyl}-1H-benzimidazol-5-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate収率 75.2%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
85 °C

実験手順

Isobutyl 5-bromo-2-(2-fluoroethylamino)-1H-benzo[d]imidazole-1-carboxylate (55 mg, 0.15 mmol) and (4-{[(1,1-dimethylethyl)oxy]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (example 1, step 2) (50 mg, 0.17 mmol) were taken into dioxane (1 mL) and water (0.2 mL) followed by addition of dichloro[1,1-bis-(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (8.5 mg) and DIPEA (0.11 mL, 0.6 mmol) and the mixture was heated to 85° C. for 12 h. The mixture was then cooled and diluted with ethyl acetate then dried over anhydrous sodium sulfate and filtered through a plug of silica gel with an ethyl acetate wash. The organic solution was then concentrated to an oil. The residue was taken into THF (2 mL) followed by sequential addition of DIPEA (0.05 mL, 0.29 mmol) and isobutyl chloroformate (0.01 mL, 0.08 mmol) then the mixture was stirred for 30 minutes. The mixture was concentrated and the residue purified by silica gel chromatography (1.5:1 hexanes:ethyl acetate) to give 1,1-dimethylethyl 7-(2-[(2-fluoroethyl)amino]-1-{[(2-methylpropyl)oxy]carbonyl}-1H-benzimidazol-5-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (59.4 mg, 75% yield) as a colorless amorphous residue. MS (EI) for C28H35FN4O5: 528 (MH+).

後処理

  1. temperatureThe mixture was then cooled
  2. dry with materialthen dried over anhydrous sodium sulfate
  3. filtrationfiltered through a plug of silica gel with an ethyl acetate
  4. washwash
  5. concentrationThe organic solution was then concentrated to an oil
  6. concentrationThe mixture was concentrated
  7. customthe residue purified by silica gel chromatography (1.5:1 hexanes:ethyl acetate)

出典と根拠

ORDレコード
ord-edee7bf5a2da4fe091b14884f9b560a0
出典データセット
uspto-grants-2014_01
特許番号
US08637499B2

反応ノート

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