Triethylamine → HCID 178502354, compound

HRID 1776012Notes

Reaction equation

HRID 1776012 reaction equation
C(N(CC)CC)C.Cl.[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:17]=[C:18]([C@@H:21]3[CH2:25][CH2:24][CH2:23][NH:22]3)[NH:19][CH:20]=2)=[CH:12][CH:11]=1.[CH3:26][O:27][C:28]([NH:30][C@@H:31]([CH:35]([CH3:37])[CH3:36])[C:32](O)=[O:33])=[O:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.C(OCC)(=O)C.O>[CH3:26][O:27][C:28](=[O:29])[NH:30][C@H:31]([C:32]([N:22]1[CH2:23][CH2:24][CH2:25][C@H:21]1[C:18]1[NH:19][CH:20]=[C:16]([C:13]2[CH:12]=[CH:11][C:10]([Br:9])=[CH:15][CH:14]=2)[N:17]=1)=[O:33])[CH:35]([CH3:37])[CH3:36]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 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 178419351(S)-4-(4-Bromophenyl)-2-(pyrrolidin-2-YL)-1H-imidazole hcl

Product 1

HCID 178502354HCID 178502354, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Triethylamine (2.3 g, 11.4 mmol) was added to a solution of 4-(4-bromo-phenyl)-2-(S)-pyrrolidin-2-yl-1H-imidazole hydrochloride (2 g, 11.4 mol), (S)-2-methoxycarbonylamino-3-methyl-butyric acid (2.5 g, 7.6 mmol), and HATU (4.3 g, 11.4 mmol) in dimethylformamide (50 mL) at 0° C. under nitrogen. The reaction mixture was stirred at room temperature overnight and treated with ethyl acetate (100 mL) and water (1000 mL). The organic layer was washed with water (2×100 mL) and brine (100 mL), dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography in 1:1 petroleum ether:ethyl acetate to give the title compound (2.5 g 74% yield) as a yellow solid. 1H NMR (d6-DMSO, 400 MHz) δ (ppm) 7.63 (d, J=8.8 Hz, 2H), 7.54 (m, 1H), 7.47 (m, 2H), 7.26 (d, J=8.4 Hz, 1H), 5.03 (m, 1H), 4.02 (t, J=8.4 Hz, 1H), 3.76 (m, 2H), 3.51 (s, 3H), 2.10 (m, 2H), 1.93 (m, 3H), 0.85 (d, J=6.8 Hz, 3H), 0.81 (d, J=6.8 Hz, 3H).

Workup

  1. washThe organic layer was washed with water (2×100 mL) and brine (100 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel column chromatography in 1:1 petroleum ether

Sources & evidence

ORD record
ord-2d25f20744aa4834984ac8add5dc21b6
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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