Dichloromethane → HCID 178502118, compound

HRID 1625491Notes

Reaction equation

HRID 1625491 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH3:13])[CH2:10][C@H:9]1[C:14]1[NH:15][CH:16]=[C:17]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28](B4OC(C)(C)C(C)(C)O4)=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[N:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].I[C:41]1[CH:67]=[CH:66][C:44]2[NH:45][C:46]([C@@H:48]3[CH2:52][C@H:51]([CH3:53])[CH2:50][N:49]3[C:54]([CH:56]([N:60]([CH3:65])[C:61](=[O:64])[O:62][CH3:63])[CH:57]([CH3:59])[CH3:58])=[O:55])=[N:47][C:43]=2[CH:42]=1.C(Cl)Cl.C([O-])(O)=O.[Na+]>>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([CH3:13])[CH2:10][CH:9]1[C:14]1[NH:15][CH:16]=[C:17]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([C:41]4[CH:67]=[CH:66][C:44]5[NH:45][C:46]([C@@H:48]6[CH2:52][C@H:51]([CH3:53])[CH2:50][N:49]6[C:54](=[O:55])[C@@H:56]([N:60]([C:61]([O:62][CH3:63])=[O:64])[CH3:65])[CH:57]([CH3:59])[CH3:58])=[N:47][C:43]=5[CH:42]=4)=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[N:18]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 178461446HCID 178461446, compoundHCID 178502109HCID 178502109, compound

Product 1

HCID 178502118HCID 178502118, compoundYield 37.3%

Conditions

Temperature
80 °C

Procedure

To a suspension of (2S,4S)-4-methyl-2{-4-[4′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-4-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (211 mg, 0.3985 mmol), methyl N-[1-[(2S,4S)-2-(5-iodo-1H-benzimidazol-2-yl)-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]-N-methyl-carbamate (198.6 mg, 0.3985 mmol), Pd(DPPF)(Cl)2.CH2Cl2 (32.54 mg, 0.03985 mmol) in 2-propnaol (2.1 mL) is added 1M aqueous NaHCO3 (2 mL, 2 mmol). The reaction mixture is stirred at 80° C. for 18 hours, cooled to RT, filtered on a bed of Celite and concentrated to dryness. The residue is purified by flash column chromatography on silica gel (12 to 100% EtOAc in hexanes) to give 2S,4S)-2-{4-[4′-(2-{(2S,4S)-1-[(S)-2-(methoxycarbonyl-methyl-amino)-3-methyl-butyryl]-4-methyl-pyrrolidin-2-yl}-1H-benzoimidazol-5-yl)-biphenyl-4-yl]-1H-imidazol-2-yl}-4-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (115 mg, 37%).

Workup

  1. temperaturecooled to RT
  2. filtrationfiltered on a bed of Celite
  3. concentrationconcentrated to dryness
  4. customThe residue is purified by flash column chromatography on silica gel (12 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-63f3509fbf884e659ae429c364b18f99
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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