Diisopropylethylamine → HCID 178502431, compound

HRID 1625496Notes

Reaction equation

HRID 1625496 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:51])[N:5](C)[C@H:6]([C:10]([N:12]1[CH2:16][C@@H:15]([CH3:17])[CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([C:27]3[CH:32]=[CH:31][C:30]([C:33]4[CH:38]=[CH:37][C:36]([C:39]5[N:40]=[C:41]([C@@H:44]6[CH2:48][C@H:47]([CH3:49])[CH2:46][NH:45]6)[NH:42][CH:43]=5)=[CH:35][CH:34]=4)=[CH:29][CH:28]=3)=[CH:26][C:20]=2[N:19]=1)=[O:11])[CH:7]([CH3:9])[CH3:8].[CH3:52][O:53][C:54]([N:56]([CH3:64])[C@@H:57]([CH:61]([CH3:63])[CH3:62])[C:58]([OH:60])=O)=[O:55].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:5][C@@H:6]([CH:7]([CH3:9])[CH3:8])[C:10]([N:12]1[CH2:16][C@@H:15]([CH3:17])[CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([C:27]3[CH:28]=[CH:29][C:30]([C:33]4[CH:38]=[CH:37][C:36]([C:39]5[N:40]=[C:41]([C@@H:44]6[CH2:48][C@H:47]([CH3:49])[CH2:46][N:45]6[C:58](=[O:60])[C@@H:57]([N:56]([CH3:64])[C:54](=[O:55])[O:53][CH3:52])[CH:61]([CH3:63])[CH3:62])[NH:42][CH:43]=5)=[CH:35][CH:34]=4)=[CH:31][CH:32]=3)=[CH:26][C:20]=2[N:19]=1)=[O:11])=[O:51]

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 59166373N-(Methoxycarbonyl)-N-methyl-L-valineHCID 178502120HCID 178502120, compound

Product 1

HCID 178502431HCID 178502431, compoundYield 43.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl {(S)-2-methyl-1-[(2S,4S)-4-methyl-2-(5-{4′-[2-((2S,4S)-4-methyl-pyrrolidin-2-yl)-1H-imidazol-4-yl]-biphenyl-4-yl}-1H-benzoimidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester hydrochloride (68.7 mg, 0.0987 mmol) and (2S)-2-[methoxycarbonyl(methyl)amino]-3-methyl-butanoic acid (18.67 mg, 0.09867 mmol) in DMF (2 mL), cooled in an ice bath is sequentially added HATU (41.25 mg, 0.1085 mmol) and DIPEA (38.26 mg, 51.56 μL, 0.2960 mmol) under nitrogen atmosphere. The reaction mixture is stirred at room temperature for 5 hours, and diluted with water (6 mL). The mixture is extracted with EtOAc (5×6 mL), and the combined organic layers are washed with H2O (3×3 mL), dried over Na2SO4, filtered, and 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 methyl ((S)-1-((2S,4S)-2-(4-(4′-(2-((2S,4S)-1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-4-methylpyrrolidin-2-yl)-3H-benzo[d]imidazol-6-yl)-[1,1′-biphenyl]-4-yl)-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)(methyl)carbamate (36 mg, 41%).

Workup

  1. extractionThe mixture is extracted with EtOAc (5×6 mL)
  2. washthe combined organic layers are washed with H2O (3×3 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe residue is purified by flash column chromatography on silica gel (0 to 10% methanol in CH2Cl2)
  7. customis further purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-acbcc9b13f2a422bb0a069f0ad4f06a1
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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