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

HRID 1751333ノート

反応式

HRID 1751333 の反応式
[OH:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]2[NH:15][C:16](C3C=CC(B4OC(C)(C)C(C)(C)O4)=CC=3)=[CH:17][N:18]=2)[CH2:3]1.Br[C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[CH:41]=[C:40]([C:45]1[NH:49][C:48]([C@@H:50]3[CH2:54][CH2:53][CH2:52][N:51]3[C:55](=[O:65])[C@@H:56]([NH:60][C:61](=[O:64])[O:62][CH3:63])[CH:57]([CH3:59])[CH3:58])=[N:47][CH:46]=1)[CH:39]=[CH:38]2.C([O-])([O-])=O.[K+].[K+]>COCCOC.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>[OH:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:11])[CH3:12])=[O:8])[C@H:4]([C:14]2[NH:15][C:16]([C:35]3[CH:36]=[CH:37][C:42]([C:35]4[CH:44]=[CH:43][C:42]5[C:37](=[CH:38][CH:39]=[C:40]([C:45]6[NH:49][C:48]([C@@H:50]7[CH2:54][CH2:53][CH2:52][N:51]7[C:55](=[O:65])[C@@H:56]([NH:60][C:61]([O:62][CH3:63])=[O:64])[CH:57]([CH3:59])[CH3:58])=[N:47][CH:46]=6)[CH:41]=5)[CH:36]=4)=[CH:43][CH:44]=3)=[CH:17][N:18]=2)[CH2:3]1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 59166440Tert-butyl (2S,4S)-4-hydroxy-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)phenyl)-1H-imidazol-2-YL)pyrrolidine-1-carboxylateHCID 59610262methyl (S)-1-((S)-2-(5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

生成物 1

HCID 69675612(2S,4S)-tert-butyl 4-hydroxy-2-(5-(4-(6-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate収率 21.9%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

(2S,4S)-tert-butyl 4-hydroxy-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (200 mg, 0.44 mmol) and methyl (S)-1-((S)-2-(5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (219 mg, 0.44 mmol) were combined in DME (5 mL). Pd(PPh3)4 (51 mg, 0.0446 mmol) and K2CO3 (2M H2O, 0.73 mL, 1.45 mmol) were added, and the solution was degassed with N2 for 10 min. The solution was heated to 85° C. and stirred o/n. The following morning, the solution was cooled to rt. The solution was diluted with EtOAc, washed with sat. NaHCO3, brine, dried over MgSO4, and concentrated. The residue was purified by silica gel chromatography to yield product (36 mg).

後処理

  1. customthe solution was degassed with N2 for 10 min
  2. temperatureThe following morning, the solution was cooled to rt
  3. additionThe solution was diluted with EtOAc
  4. washwashed with sat. NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-11b5914623dd457983e0031cb75195db
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

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