Diisopropylethylamine → HCID 117607804, compound

HRID 58816Notes

Reaction equation

HRID 58816 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH2:9][C@H:10]([NH:14][C:15](=[O:28])[C@@H:16]([NH:18][C:19](=[O:27])[CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH3:17])[C:11](O)=[O:12])[CH:5]=[CH:6][C:7]=1[CH3:8].[NH2:29][C@@H:30]([CH2:37][CH:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1)[C:31]([C@@:33]1([CH3:36])[CH2:35][O:34]1)=[O:32].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.CCOC(C)=O>[CH:38]1([CH2:37][C@H:30]([NH:29][C:11](=[O:12])[C@@H:10]([NH:14][C:15](=[O:28])[C@@H:16]([NH:18][C:19](=[O:27])[CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH3:17])[CH2:9][C:4]2[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([OH:1])[CH:3]=2)[C:31]([C@@:33]2([CH3:36])[CH2:35][O:34]2)=[O:32])[CH2:42][CH2:41][CH2:40][CH2:39]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 117607800HCID 117607800, compoundHCID 117690776HCID 117690776, compound

Product 1

HCID 117607804HCID 117607804, compoundYield 11%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-3-(3-Hydroxy-4-methylphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanoic acid was dissolved in DMF (5 mL) and (S)-2-amino-3-cyclopentyl-1-((R)-2-methyloxiran-2-yl)propan-1-one (TFA salt, 0.40 g, 1.3 mmol), HATU (0.65 g, 1.9 mmol) and DIEA (0.5 mL) were added at 0° C. with stirring. The reaction mixture was allowed to warm to ambient temperature and stirred for 3 h. EtOAc (100 mL) and water (100 mL) was added and the two layers were separated. The aqueous phase was extracted with EtOAc (30 mL×3) and the combined organic phases were washed with brine (50 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (DCM/EtOAc/MeOH=20:10:1) to afford (S)-N-((S)-3-cyclopentyl-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-(3-hydroxy-4-methylphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanamide (150 mg, 11% yield over three steps). 1H NMR (300 MHz, DMSO-d6): δ 9.06 (s, 1H), 8.26 (d, J=7.2 Hz, 1H), 8.06 (d, J=8.7 Hz, 1H), 7.75 (d, J=7.5 Hz, 1H), 6.89 (d, J=7.8 Hz, 1H), 6.61 (s, 1H), 6.53 (d, J=7.2 Hz, 1H), 4.51-4.39 (m, 1H), 4.30-4.15 (m, 2H), 3.69-3.61 (m, 4H), 3.17 (d, J=5.4 Hz, 1H), 3.00 (d, J=5.1 Hz, 1H), 2.90-2.81 (m, 3H), 2.42-2.30 (m, 4H), 2.04 (s, 3H), 1.91-1.42 (m, 7H), 1.41 (s, 3H), 1.30-1.02 (m, 6H). MS(EI) for C30H44N4O7, found 573.3 (MH)+.

Workup

  1. stirringstirred for 3 h
  2. customthe two layers were separated
  3. extractionThe aqueous phase was extracted with EtOAc (30 mL×3)
  4. washthe combined organic phases were washed with brine (50 mL×3)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel (DCM/EtOAc/MeOH=20:10:1)

Sources & evidence

ORD record
ord-83927a0df5904c75a5d3fc66172a8cd8
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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