Diisopropylethylamine → HCID 178502357, compound

HRID 1625505Notes

Reaction equation

HRID 1625505 reaction equation
[Cl-].[CH3:2][O:3][C:4]([NH:6][C@@H:7]([CH:40]([CH3:42])[CH3:41])[C:8]([N:10]1[CH2:14][CH2:13][CH2:12][C@H:11]1[C:15]1[NH:19][C:18]2[CH:20]=[CH:21][C:22]([C:24]3[CH:29]=[CH:28][C:27]([C:30]4[NH+:31]=[C:32]([C@@H:35]5[CH2:39][CH2:38][CH2:37][NH2+:36]5)[NH:33][CH:34]=4)=[CH:26][CH:25]=3)=[CH:23][C:17]=2[N:16]=1)=[O:9])=[O:5].[Cl-].[CH3:44][O:45][C:46]([NH:48][C@@H:49]([CH:53]([CH3:55])[CH3:54])[C:50](O)=[O:51])=[O:47].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH3:2][O:3][C:4]([NH:6][C@@H:7]([CH:40]([CH3:42])[CH3:41])[C:8]([N:10]1[CH2:14][CH2:13][CH2:12][C@H:11]1[C:15]1[NH:19][C:18]2[CH:20]=[CH:21][C:22]([C:24]3[CH:25]=[CH:26][C:27]([C:30]4[N:31]=[C:32]([C@@H:35]5[CH2:39][CH2:38][CH2:37][N:36]5[C:50]([C@@H:49]([NH:48][C:46](=[O:47])[O:45][CH3:44])[CH:53]([CH3:55])[CH3:54])=[O:51])[NH:33][CH:34]=4)=[CH:28][CH:29]=3)=[CH:23][C:17]=2[N:16]=1)=[O:9])=[O:5]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 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 178502337HCID 178502337, compound

Product 1

HCID 178502357HCID 178502357, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
2 °C

Procedure

To a cold (0-4° C.) stirred light suspension of 4-(4-(2-((S)-1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-5-yl)phenyl)-2-((S)-pyrrolidin-1-ium-2-yl)-1H-imidazol-3-ium chloride (98.09 mg, 0.15 mmol) and (2S)-2-(methoxycarbonylamino)-3-methyl-butanoic acid (28.91 mg, 0.1650 mmol) in DMF (1.5 mL) is sequentially added HATU (85.55 mg, 0.2250 mmol) and DIPEA (116.3 mg, 156.7 μL, 0.9000 mmol). The resulting mixture is slowly warmed up to rt, stirred overnight, then diluted with water (5 mL), extracted with ethyl acetate (3×6 mL). The combined extracts are washed with saturated bicarbonate solution, brine, dried (Na2SO4) and concentrated. Residue purified on 25+M biotage SiO2 cartridge using MeOH-EtOAc (0:100, 15:85) as eluent to afford methyl N-[(1S)-1-[(2S)-2-[4-[4-[2-[(2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (45.8 mg, 0.06007 mmol, 37.45%) as white solid. This product is repurified by reverse phase HPLC to give methyl N-[(1S)-1-[(2S)-2-[4-[4-[2-[(2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (29.6 mg) as white solid.

Workup

  1. temperatureThe resulting mixture is slowly warmed up to rt
  2. stirringstirred overnight
  3. extractionextracted with ethyl acetate (3×6 mL)
  4. washThe combined extracts are washed with saturated bicarbonate solution, brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customResidue purified on 25+M biotage SiO2 cartridge

Sources & evidence

ORD record
ord-c174a814c10344b2a9e79f1ed1a62015
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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