Diisopropylethylamine → HCID 178502121, compound

HRID 1625493Notes

Reaction equation

HRID 1625493 reaction equation
[CH3:1][O:2][C:3]([N:5]([CH3:13])[C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7](O)=[O:8])=[O:4].Cl.[CH3:15][N:16]([C@@H:21]([CH:62]([CH3:64])[CH3:63])[C:22]([N:24]1[CH2:28][C@@H:27]([CH3:29])[CH2:26][C@H:25]1[C:30]1[NH:34][C:33]2[CH:35]=[C:36]([C:39]3[CH:44]=[CH:43][C:42]([C:45]4[CH:50]=[CH:49][C:48]([C:51]5[NH:55][C:54]([C@@H:56]6[CH2:60][C@H:59]([CH3:61])[CH2:58][NH:57]6)=[N:53][CH:52]=5)=[CH:47][CH:46]=4)=[CH:41][CH:40]=3)[CH:37]=[CH:38][C:32]=2[N:31]=1)=[O:23])[C:17](=[O:20])[O:18][CH3:19].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.C([O-])(O)=O.[Na+]>[CH3:19][O:18][C:17]([N:16]([CH3:15])[C@@H:21]([CH:62]([CH3:64])[CH3:63])[C:22]([N:24]1[CH2:28][C@@H:27]([CH3:29])[CH2:26][C@H:25]1[C:30]1[NH:31][C:32]2[CH:38]=[CH:37][C:36]([C:39]3[CH:40]=[CH:41][C:42]([C:45]4[CH:50]=[CH:49][C:48]([C:51]5[N:55]=[C:54]([C@@H:56]6[CH2:60][C@H:59]([CH3:61])[CH2:58][N:57]6[C:7]([C@@H:6]([N:5]([CH3:13])[C:3](=[O:4])[O:2][CH3:1])[CH:10]([CH3:12])[CH3:11])=[O:8])[NH:53][CH:52]=5)=[CH:47][CH:46]=4)=[CH:43][CH:44]=3)=[CH:35][C:33]=2[N:34]=1)=[O:23])=[O:20]

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 67413654Methyl-{(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

Product 1

HCID 178502121HCID 178502121, compoundYield 42.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (2S)-2-[methoxycarbonyl(methyl)amino]-3-methyl-butanoic acid (12.8 mg, 0.06765 mmol) and methyl methyl((S)-3-methyl-1-((2S,4S)-4-methyl-2-(6-(4′-(2-((2S,4S)-4-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)[1,1′-biphenyl]-4-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-1-oxobutan-2-yl)carbamate hydrochloride (48.1 mg, 0.0677 mmol) in DMF (2 mL) cooled in an ice bath is sequentially added HATU (28.3 mg, 0.0744 mmol) and DIPEA (0.035 mL, 0.203 mmol) under nitrogen atmosphere. The reaction mixture is stirred at room temperature for 19 hours and diluted with saturated aqueous NaHCO3 (2 mL). The mixture is extracted with EtOAc (5×3 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 reverse phase preparative HPLC to give methyl N-[(1S)-1-[(2S,4S)-2-[4-[4-[4-[2-[(2S,4S)-1-[(2S)-2-[methoxycarbonyl(methyl)amino]-3-methyl-butanoyl]-4-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]-N-methyl-carbamate (24.4 mg, 41%).

Workup

  1. extractionThe mixture is extracted with EtOAc (5×3 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 reverse phase preparative HPLC

Sources & evidence

ORD record
ord-b843837a9b0c4569b8e57437bcbba786
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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