2,4,6-Trimethylpyridine → HCID 178502201, compound

HRID 1625507Notes

Reaction equation

HRID 1625507 reaction equation
[CH3:1][CH:2]([CH3:49])[CH:3]([NH:44][C:45](=[O:48])[O:46][CH3:47])[C:4]([N:6]1[C@H:10]([C:11]2[NH:15][C:14]3[CH:16]=[CH:17][CH:18]=[C:19]([C:20]4[CH:25]=[CH:24][C:23]([C:26]5[CH:31]=[CH:30][C:29]([C:32]6[NH:36][C:35]([C@@H:37]7[CH2:41][CH2:40][C@H:39]([CH3:42])[NH:38]7)=[N:34][CH:33]=6)=[CH:28][CH:27]=5)=[CH:22][CH:21]=4)[C:13]=3[N:12]=2)[CH2:9][CH2:8][C@@H:7]1[CH3:43])=[O:5].[CH3:50][O:51][C:52]([NH:54][C@@H:55]([CH:59]([CH3:61])[CH3:60])[C:56](O)=[O:57])=[O:53].N1C(C)=CC(C)=CC=1C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH3:47][O:46][C:45]([NH:44][CH:3]([CH:2]([CH3:49])[CH3:1])[C:4]([N:6]1[C@@H:7]([CH3:43])[CH2:8][CH2:9][C@H:10]1[C:11]1[NH:12][C:16]2[CH:17]=[CH:18][C:19]([C:20]3[CH:25]=[CH:24][C:23]([C:26]4[CH:31]=[CH:30][C:29]([C:32]5[N:36]=[C:35]([C@@H:37]6[CH2:41][CH2:40][C@H:39]([CH3:42])[N:38]6[C:56]([C@@H:55]([NH:54][C:52](=[O:53])[O:51][CH3:50])[CH:59]([CH3:61])[CH3:60])=[O:57])[NH:34][CH:33]=5)=[CH:28][CH:27]=4)=[CH:22][CH:21]=3)=[CH:13][C:14]=2[N:15]=1)=[O:5])=[O:48]

Participants

7

Reactant 4

HCID 79532,4,6-TrimethylpyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 67414079HCID 67414079, compound

Product 1

HCID 178502201HCID 178502201, compoundYield 21.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of methyl N-[2-methyl-1-[(2S,5S)-2-methyl-5-[4-[4-[4-[2-[(2S,5S)-5-methylpyrrolidin-2-yl]-1H-imidazol-5-yl]phenyl]phenyl]-1H-benzimidazol-2-yl]pyrro-lidine-1-carbonyl]propyl]carbamate (88 mg, 0.126 mmol), (2S)-2-(methoxycarbonylamino)-3-methyl-butanoic acid (22 mg, 0.126 mmol) and 2,4,6-collidine (50.11 μl, 0.38 mmol) in DMF (3.5 ml) is added HATU (52.8 mg, 0.14 mmol) at 0° C. The reaction mixture is stirred at rt for 5 hours, 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 20% MeOH in CH2Cl2) and repurified by reverse phase HPLC using a gradient of CH3CN/water to afford the methyl N-[(1S)-1-[(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-carbonyl]-2-methyl-propyl]carbamate (22 mg, 19.9%) as a white fluffy powder.

Workup

  1. washwashed with H2O and brine
  2. dry with materialThe organic phase is dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by flash column chromatography on silica gel (1 to 20% MeOH in CH2Cl2)
  6. customrepurified by reverse phase HPLC

Sources & evidence

ORD record
ord-b4f8df2a21314e98a4f15ee922362298
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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