Dichloromethane → HCID 178502202, 화합물

HRID 1625506노트

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HRID 1625506 반응식
[CH3:1][C@H:2]1[CH2:6][CH2:5][C@@H:4]([C:7]2[NH:8][CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4[CH:23]=[CH:22][C:21](B5OC(C)(C)C(C)(C)O5)=[CH:20][CH:19]=4)=[CH:14][CH:13]=3)[N:11]=2)[N:3]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].I[C:41]1[CH:66]=[CH:65][C:44]2[NH:45][C:46]([C@@H:48]3[CH2:52][CH2:51][C@H:50]([CH3:53])[N:49]3[C:54]([C@@H:56]([NH:60]C(=O)OC)[CH:57]([CH3:59])[CH3:58])=[O:55])=[N:47][C:43]=2[CH:42]=1.[CH2:67](Cl)Cl.[C:70]([O-:73])([OH:72])=O.[Na+]>CC(O)C>[CH3:67][O:72][C:70]([NH:60][CH:56]([CH:57]([CH3:58])[CH3:59])[C:54]([N:49]1[C@@H:50]([CH3:53])[CH2:51][CH2:52][C@H:48]1[C:46]1[NH:47][C:43]2[CH:42]=[CH:41][C:66]([C:21]3[CH:20]=[CH:19][C:18]([C:15]4[CH:14]=[CH:13][C:12]([C:10]5[N:11]=[C:7]([C@@H:4]6[CH2:5][CH2:6][C@H:2]([CH3:1])[N:3]6[C:33]([O:35][C:36]([CH3:39])([CH3:37])[CH3:38])=[O:34])[NH:8][CH:9]=5)=[CH:17][CH:16]=4)=[CH:23][CH:22]=3)=[CH:65][C:44]=2[N:45]=1)=[O:55])=[O:73]

참가 물질

6

반응물 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 178461190HCID 178461190, 화합물HCID 178502496HCID 178502496, 화합물

생성물 1

HCID 178502202HCID 178502202, 화합물수율 375.4%

시약·촉매·용매 1

HCID 3776Isopropanol용매

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온도
80 °C

실험 절차

To a mixture of tert-butyl (2S,5S)-2-methyl-5-[4-[4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carboxylate (180 mg, 0.34 mmol), methyl N-[(1S)-1-[(2S,5S)-2-(5-iodo-1H-benzimidazol-2-yl)-5-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (164.7 mg, 0.34 mmol), Pd(dppf)(Cl)2.CH2Cl2 (27.77 mg, 0.034 mmol) in 2-propanol (2 ml) is added aq NaHCO3 (1.7 mL of 1 M, 1.7 mmol). The reaction mixture is purged with N2, heated at 80° C. overnight, diluted with EtOAc, washed with H2O and brine. The organic phase is dried over Na2SO4, filtered and concentrated. The residue is purified by flash column chromatography on silica gel (1 to 30% MeOH in CH2Cl2) to afford the tert-butyl (2S,5S)-2-[4-[4-[4-[2-[(2S,5S)-1-[2-(methoxycarbonylamino)-3-methyl-butanoyl]-5-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]-5-methyl-pyrrolidine-1-carboxylate (97 mg, 37.5%) as a beige solid.

후처리

  1. customThe reaction mixture is purged with N2
  2. additiondiluted with EtOAc
  3. washwashed with H2O and brine
  4. dry with materialThe organic phase is dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by flash column chromatography on silica gel (1 to 30% MeOH in CH2Cl2)

출처 및 근거

ORD 기록
ord-6687cbd616bb4a14a293b9c6943a2265
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08779156B2

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