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Potassium Carbonate → tert-butyl 3-(6-(3-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-6H-benzo[c]chromen-8-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate

HRID 1751393
ノート
印刷プレビュー

反応式

HRID 1751393 の反応式
[CH3:1][CH:2]([CH3:44])[CH:3]([NH:39][C:40](=[O:43])[O:41][CH3:42])[C:4](=[O:38])[N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:24]=[C:23]3[C:18]([C:19]4[CH:28]=[CH:27][C:26](B5OC(C)(C)C(C)(C)O5)=[CH:25][C:20]=4[CH2:21][O:22]3)=[CH:17][CH:16]=2)=[CH:13][N:14]=1.Br[C:46]1[CH:47]=[CH:48][C:49]2[N:53]=[C:52]([C@@H:54]3[C@@H:59]4[CH2:60][C@@H:56]([CH2:57][CH2:58]4)[N:55]3[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[NH:51][C:50]=2[CH:68]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.CN(C)C=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.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]>[CH3:42][O:41][C:40]([NH:39][C@@H:3]([CH:2]([CH3:44])[CH3:1])[C:4]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:24]=[C:23]3[C:18]([C:19]4[CH:28]=[CH:27][C:26]([C:47]5[CH:46]=[CH:68][C:50]6[N:51]=[C:52]([CH:54]7[C@@H:59]8[CH2:60][CH:56]([CH2:57][CH2:58]8)[N:55]7[C:61]([O:63][C:64]([CH3:66])([CH3:65])[CH3:67])=[O:62])[NH:53][C:49]=6[CH:48]=5)=[CH:25][C:20]=4[CH2:21][O:22]3)=[CH:17][CH:16]=2)=[CH:13][N:14]=1)=[O:38])=[O:43].[CH3:42][O:41][C:40]([NH:39][C@@H:3]([CH:2]([CH3:44])[CH3:1])[C:4]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:24]=[C:23]3[C:18]([C:19]4[CH:28]=[CH:27][C:26]([C:47]5[CH:46]=[CH:68][C:50]6[N:51]=[C:52]([CH:54]7[CH:59]8[CH2:60][CH:56]([CH2:57][CH2:58]8)[N:55]7[C:61]([O:63][C:64]([CH3:66])([CH3:65])[CH3:67])=[O:62])[NH:53][C:49]=6[CH:48]=5)=[CH:25][C:20]=4[CH2:21][O:22]3)=[CH:17][CH:16]=2)=[CH:13][N:14]=1)=[O:38])=[O:43]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 3

HCID 11430Potassium CarbonateHCID 675058682-Azabicyclo(2.2.1)heptane-2-carboxylic acid, 3-(6-bromo-1H-benzimidazol-2-yl)-, 1,1-dimethylethyl ester, (1R,3S,4S)-HCID 69675075methyl 3-methyl-1-oxo-1-((S)-2-(5-(8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6H-benzo[c]chromen-3-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate

生成物 2

HCID 69675206
(4S)-tert-butyl 3-(6-(3-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-6H-benzo[c]chromen-8-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate
HCID 86708726tert-butyl 3-(6-(3-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-6H-benzo[c]chromen-8-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate収率 171%

試薬・触媒・溶媒 4

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

To a solution of methyl 3-methyl-1-oxo-1-((S)-2-(5-(8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6H-benzo[c]chromen-3-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate (196 mg, 0.32 mmol), (1R,3S,4S)-tert-butyl 3-(6-bromo-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (166 mg, 0.42 mmol), tetrakis(triphenylphosphine) palladium(0) (10 mg, 0.01 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (12 mg, 0.02 mmol) in a mixture of 1,2-dimethoxyethane (5 mL) and dimethylformamide (1 mL) was added a solution of potassium carbonate (2M in water, 0.51 mL, 0.31 mmol). The resulting mixture was degassed and then heated to 85° C. under argon for 18 hours. After cooling to room temperature, the reaction was diluted with ethyl acetate. The organics were washed with water and brine, dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography to yield S)-tert-butyl 4S)-tert-butyl 3-(6-(3-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-6H-benzo[c]chromen-8-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (215 mg, 85%) LCMS-ESI+: calculated for C45H51N7O6: 785.95; observed [M+1]+: 786.43.

後処理

  1. customThe resulting mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction was diluted with ethyl acetate
  4. washThe organics were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography

出典と根拠

ORDレコード
ord-3a48c357756241a5bd40a50962f79ca4
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09156823B2

反応ノート

読み込み中…

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