Dichloromethane → HCID 178502202, compound

HRID 1625506Notes

Reaction equation

HRID 1625506 reaction equation
[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]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 178461190HCID 178461190, compoundHCID 178502496HCID 178502496, compound

Product 1

HCID 178502202HCID 178502202, compoundYield 375.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-6687cbd616bb4a14a293b9c6943a2265
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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