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Potassium Carbonate → (S)-tert-butyl 2-(5-(4-(6-(2-((S)-1-((2S,3R)-3-(difluoromethoxy)-2-(methoxycarbonylamino)butanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

HRID 1751359
ノート
印刷プレビュー

反応式

HRID 1751359 の反応式
[F:1][CH:2]([F:43])[O:3][C@H:4]([CH3:42])[C@H:5]([NH:37][C:38](=[O:41])[O:39][CH3:40])[C:6](=[O:36])[N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[C:12]1[NH:13][C:14]([C:17]2[CH:26]=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[C:22](B4OC(C)(C)C(C)(C)O4)[CH:23]=3)[CH:18]=2)=[CH:15][N:16]=1.Br[C:45]1[CH:50]=[CH:49][C:48]([C:51]2[NH:55][C:54]([C@@H:56]3[CH2:60][CH2:59][CH2:58][N:57]3[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])=[N:53][CH:52]=2)=[CH:47][CH:46]=1.C(=O)([O-])[O-].[K+].[K+]>C(COC)OC>[F:1][CH:2]([F:43])[O:3][C@H:4]([CH3:42])[C@H:5]([NH:37][C:38]([O:39][CH3:40])=[O:41])[C:6]([N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[C:12]1[NH:13][C:14]([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[CH:23]=[C:22]([C:45]2[CH:46]=[CH:47][C:48]([C:51]4[NH:55][C:54]([C@@H:56]5[CH2:60][CH2:59][CH2:58][N:57]5[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])=[N:53][CH:52]=4)=[CH:49][CH:50]=2)[CH:21]=[CH:20]3)=[CH:15][N:16]=1)=[O:36]
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

5

反応物 3

HCID 11430Potassium CarbonateHCID 56605031(S)-tert-butyl 2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 67681934methyl (2S,3R)-3-(difluoromethoxy)-1-oxo-1-((S)-2-(5-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate

生成物 1

HCID 86708711
(S)-tert-butyl 2-(5-(4-(6-(2-((S)-1-((2S,3R)-3-(difluoromethoxy)-2-(methoxycarbonylamino)butanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate
収率 45%

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

To a solution of methyl (2S,3R)-3-(difluoromethoxy)-1-oxo-1-((S)-2-(5-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate (120 mg, 0.20 mmol), (S)-tert-butyl 2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (87 mg, 0.22 mmol), and tetrakistriphenylphosphine palladium(0) (23 mg, 0.020 mmol) in dimethoxyethane (2 mL) was added a 2M aqueous potassium carbonate solution (0.40 mL, 0.80 mmol). The mixture was degassed with a stream of argon for 15 minutes, and then heated to 85° C. for three hours. The reaction was diluted with ethyl acetate, cooled to room temperature and filtered through Celite. The filtrate was washed with water and brine, dried (MgSO4) and concentrated. The resulting residue was purified by flash chromatography to yield (S)-tert-butyl 2-(5-(4-(6-(2-((S)-1-((2S,3R)-3-(difluoromethoxy)-2-(methoxycarbonylamino)butanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (70 mg, 45%). LCMS-ESI+: calculated for C42H47F2N7O6: 783.86. observed [M+1]+: 784.72.

後処理

  1. customThe mixture was degassed with a stream of argon for 15 minutes
  2. additionThe reaction was diluted with ethyl acetate
  3. temperaturecooled to room temperature
  4. filtrationfiltered through Celite
  5. washThe filtrate was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe resulting residue was purified by flash chromatography

出典と根拠

ORDレコード
ord-b2cf7902d2174788ae35b46fd3a74269
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

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート