Diisopropylethylamine → Succinamide peptidomimetic, 20

HRID 2249953Notes

Reaction equation

HRID 2249953 reaction equation
[CH:1]1([CH2:7][CH2:8][C@H:9]([CH2:13][C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:15])[C:10]([OH:12])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:46][C:47]([F:61])([F:60])[O:48][C:49]1[CH:54]=[CH:53][C:52]([NH:55][CH2:56][C@@H:57]([NH2:59])[CH3:58])=[CH:51][CH:50]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.C(Cl)Cl>[CH:1]1([CH2:7][CH2:8][C@H:9]([CH2:13][C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:15])[C:10]([NH:59][C@@H:57]([CH3:58])[CH2:56][NH:55][C:52]2[CH:51]=[CH:50][C:49]([O:48][C:47]([F:46])([F:60])[F:61])=[CH:54][CH:53]=2)=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

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 59733160HCID 59733160, compoundHCID 68478396HCID 68478396, compound

Product 1

HCID 11329727Succinamide peptidomimetic, 20

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(R)-(2-Cyclohexyl-ethyl)-4-morpholin-4-yl-4-oxo-butyric acid (98 mg, 0.33 mmol, 1.0 eq.) dissolved in DMF (2 mL) and treated with HATU (137 mg, 0.36 mmol, 1.1 eq.), (S)-N1-(4-Trifluoromethoxy-phenyl)-propane-1,2-diamine (85 mg, 0.36 mmol, 1.1 eq.) and DIPEA (63 μL, 0.36 mmol, 1.1 eq.). Alternatively CH2Cl2 can be used as the reaction solvent based on starting material solubility. The reaction is monitored by LC/MS. The reaction mixture is diluted with ethyl acetate (20 mL) and extracted with 0.5 M HCl (2×10 mL), saturated NaHCO3, and brine. The organic layer is dried over MgSO4, filtered and evaporated. Alternatively, the crude reaction can be directly purified by mass-directed HPLC. Mass-directed HPLC provides the title compound as a white solid after evaporation and lyophilization: 1H NMR (CD3OD, 400 MHz) δ 0.74-0.82 (m, 2H), 1.08-1.65 (m, 13H), 1.21(d, J=6.8 Hz, 3H), 2.38(dd, J=4.8, 15.6 Hz, 1H), 2.65(m, 1H), 2.74(dd, J=9.6, 15.6 Hz, 1H), 3.10(m, 2H), 3.54-3.66(m, 8H), 4.11(m, 1H), 6.45(m, 2H), 6.97(m, 2H). HPLC-MS calcd. for C26H38F3N3O4 (M+H+) 514.3. found 514.2.

Workup

  1. extractionextracted with 0.5 M HCl (2×10 mL), saturated NaHCO3, and brine
  2. dry with materialThe organic layer is dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customAlternatively, the crude reaction
  6. customcan be directly purified by mass-directed HPLC

Sources & evidence

ORD record
ord-353ce26bc88648e9893f635bcd29d0a1
Source dataset
uspto-grants-2008_01
Patent number
US07314872B2

Reaction notes

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