Dichloromethane → HCID 178461451, 화합물

HRID 1625511노트

반응식

HRID 1625511 반응식
I[C:2]1[CH:23]=[CH:22][C:5]2[NH:6][C:7]([C@@H:9]3[CH2:13][C@H:12]([CH3:14])[CH2:11][N:10]3[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[N:8][C:4]=2[CH:3]=1.[C:24]([C:26]1[CH:31]=[CH:30][C:29]([C:32]2[N:33]=[C:34]([C@@H:37]3[CH2:41][C@H:40]([CH3:42])[CH2:39][N:38]3[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[NH:35][CH:36]=2)=[CH:28][CH:27]=1)#[CH:25].C(Cl)Cl>CN(C=O)C.[Cu]I>[C:18]([O:17][C:15]([N:10]1[CH2:11][C@@H:12]([CH3:14])[CH2:13][C@H:9]1[C:7]1[NH:6][C:5]2[CH:22]=[CH:23][C:2]([C:25]#[C:24][C:26]3[CH:31]=[CH:30][C:29]([C:32]4[N:33]=[C:34]([C@@H:37]5[CH2:41][C@H:40]([CH3:42])[CH2:39][N:38]5[C:43]([O:45][C:46]([CH3:47])([CH3:49])[CH3:48])=[O:44])[NH:35][CH:36]=4)=[CH:28][CH:27]=3)=[CH:3][C:4]=2[N:8]=1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

참가 물질

6

반응물 3

HCID 6344DichloromethaneHCID 178435838HCID 178435838, 화합물HCID 178461441HCID 178461441, 화합물

생성물 1

HCID 178461451HCID 178461451, 화합물수율 66.2%

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6228Dimethylformamide용매

실험 절차

To a solution of tert-butyl (2S,4S)-2-(5-iodo-1H-benzimidazol-2-yl)-4-methyl-pyrrolidine-1-carboxylate (68.5 mg, 0.16 mmol) in DMF (3 mL) are sequentially added tert-butyl (2S,4S)-2-[4-(4-ethynylphenyl)-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carboxylate (47 mg, 0.13 mmol), Pd(DPPF)(Cl)2.CH2Cl2 (5.4 mg, 0.0067 mmol). The mixture is degassed well under vacuum and to it is added TEA (37 uL, 0.27 mmol), followed by CuI (1.2 mg, 0.0067 mmol). Then the reaction mixture is stirred under nitrogen at rt overnight. After removal of the solvent, the crude is purified by flash column chromatography on silica gel using methanol/CH2Cl2 0-5% to obtain tert-butyl (2S,4S)-2-[4-[4-[2-[2-[(2S,4S)-1-tert-butoxycarbonyl-4-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]ethynyl]phenyl]-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carboxylate (56 mg, 64%).

후처리

  1. customThe mixture is degassed well under vacuum and to it
  2. customAfter removal of the solvent
  3. customthe crude is purified by flash column chromatography on silica gel

출처 및 근거

ORD 기록
ord-eb0c27234095481799961ed2036c5725
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08779156B2

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