Dichloromethane → HCID 178502202, Verbindung

HRID 1625506Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1625506
[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]

Komponenten

6

Edukt 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 178461190HCID 178461190, VerbindungHCID 178502496HCID 178502496, Verbindung

Produkt 1

HCID 178502202HCID 178502202, VerbindungAusbeute 375,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-6687cbd616bb4a14a293b9c6943a2265
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08779156B2

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