Dichloromethane → HCID 178502202、化合物

HRID 1625506ノート

反応式

HRID 1625506 の反応式
[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]

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 178461190HCID 178461190、化合物HCID 178502496HCID 178502496、化合物

生成物 1

HCID 178502202HCID 178502202、化合物収率 375.4%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-6687cbd616bb4a14a293b9c6943a2265
出典データセット
uspto-grants-2014_07
特許番号
US08779156B2

反応ノート

読み込み中…