Dichloromethane → HCID 178502438, compound

HRID 1625498Notes

Reaction equation

HRID 1625498 reaction equation
I[C:2]1[CH:27]=[CH:26][C:5]2[NH:6][C:7]([C@@H:9]3[CH2:13][C@H:12]([CH3:14])[CH2:11][N:10]3[C:15]([C@@H:17]([NH:21][C:22](=[O:25])[O:23][CH3:24])[CH:18]([CH3:20])[CH3:19])=[O:16])=[N:8][C:4]=2[CH:3]=1.I[C:29]1[N:30]=[C:31]([C@@H:34]2[CH2:38][C@H:37]([CH3:39])[CH2:36][N:35]2[C:40](=[O:50])[C@@H:41]([NH:45][C:46](=[O:49])[O:47][CH3:48])[CH:42]([CH3:44])[CH3:43])[NH:32][CH:33]=1.B(O)(O)[C:52]1[CH:57]=[CH:56][C:55]([C:58]2[CH:63]=[CH:62][C:61](B(O)O)=[CH:60][CH:59]=2)=[CH:54][CH:53]=1.C(Cl)Cl.C([O-])(O)=O.[Na+]>CC(O)C>[CH3:24][O:23][C:22](=[O:25])[NH:21][C@H:17]([C:15]([N:10]1[CH2:11][C@@H:12]([CH3:14])[CH2:13][C@H:9]1[C:7]1[NH:6][C:5]2[CH:26]=[CH:27][C:2]([C:61]3[CH:62]=[CH:63][C:58]([C:55]4[CH:56]=[CH:57][C:52]([C:29]5[N:30]=[C:31]([C@@H:34]6[CH2:38][C@H:37]([CH3:39])[CH2:36][N:35]6[C:40](=[O:50])[C@@H:41]([NH:45][C:46]([O:47][CH3:48])=[O:49])[CH:42]([CH3:44])[CH3:43])[NH:32][CH:33]=5)=[CH:53][CH:54]=4)=[CH:59][CH:60]=3)=[CH:3][C:4]=2[N:8]=1)=[O:16])[CH:18]([CH3:20])[CH3:19]

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 27346084,4'-Biphenyldiboronic AcidHCID 178502434HCID 178502434, compoundHCID 178502451HCID 178502451, compound

Product 1

HCID 178502438HCID 178502438, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a suspension of methyl N-[(1S)-1-[(2S,4S)-2-(5-iodo-1H-benzimidazol-2-yl)-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (52.40 mg, 0.1082 mmol), methyl ((S)-1-((2S,4S)-2-(4-iodo-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate (47 mg, 0.1082 mmol), [1,1′-biphenyl]-4,4′-diyldiboronic acid (26.17 mg, 0.1082 mmol), Pd(DPPF)(Cl)2.CH2Cl2 (4.418 mg, 0.005410 mmol) and 1 mL of 2-propanol in a microwave vial is added 1M aqueous NaHCO3 (541.0 μL, 0.5410 mmol). The reaction mixture is stirred for 3 minutes at room temperature and is heated to 150° C. in the microwave for 10 minutes. The reaction mixture is concentrated to dryness. The residue is purified by flash column chromatography on silica gel (0 to 10% methanol in CH2Cl2) and is further purified by reverse phase preparative HPLC to give ((S)-1-{(2S,4S)-2-[5-(4′-{2-[(2S,4S)-1-((S)-2-methoxycarbonylamino-3-methyl-butyryl)-4-methyl-pyrrolidin-2-yl]-1H-imidazol-4-yl}-biphenyl-4-yl)-1H-benzoimidazol-2-yl]-4-methyl-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (12 mg, 25%).

Workup

  1. temperatureis heated to 150° C. in the microwave for 10 minutes
  2. concentrationThe reaction mixture is concentrated to dryness
  3. customThe residue is purified by flash column chromatography on silica gel (0 to 10% methanol in CH2Cl2)
  4. customis further purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-7c608e63c723487e9e3beeca2f85a36f
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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