HCID 117607964, compound → (S)-3-hydroxy-N-((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)-2-(2-morpholinoacetamido)propanamide

HRID 58922Notes

Reaction equation

HRID 58922 reaction equation
C([O:8][CH2:9][C@H:10]([NH:41][C:42](=[O:50])[CH2:43][N:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1)[C:11]([NH:13][C@@H:14]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1)[C:15]([NH:17][C@@H:18]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:19]([C@@:21]1([CH3:24])[CH2:23][O:22]1)=[O:20])=[O:16])=[O:12])C1C=CC=CC=1>[Pd].CO>[OH:8][CH2:9][C@H:10]([NH:41][C:42](=[O:50])[CH2:43][N:44]1[CH2:45][CH2:46][O:47][CH2:48][CH2:49]1)[C:11]([NH:13][C@@H:14]([CH2:32][C:33]1[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=1)[C:15]([NH:17][C@@H:18]([CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:19]([C@@:21]1([CH3:24])[CH2:23][O:22]1)=[O:20])=[O:16])=[O:12]

Participants

4

Reactant 1

HCID 117607964HCID 117607964, compound

Product 1

HCID 117608053(S)-3-hydroxy-N-((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)-2-(2-morpholinoacetamido)propanamideYield 41,550%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

To (S)-3-(benzyloxy)-N-((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)-2-(2-morpholinoacetamido)propanamide (330 mg, 0.480 μmol) was added methanol (20 mL) and Pd/C (10%, 500 mg). The reaction mixture was stirred under a hydrogen atmosphere (balloon) for 16 h at 40° C. before it was cooled to ambient temperature and filtered through Celite. Purification by column chromatography (3:1 DCM/ethyl acetate+0-10% methanol) provided (S)-3-hydroxy-N-((S)-3-(4-methoxyphenyl)-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)-2-(2-morpholinoacetamido)propanamide (119 mg, 42%) as a colorless amorphous solid. 1H NMR (400 MHz,) δ 7.89 (d, J=7.7 Hz, 1H), 7.26-7.19 (m, 3H), 7.10-7.06 (m, 2H), 7.01-6.96 (m, 2H), 6.82-6.79 (m, 2H), 6.73 (d, J=8.0 Hz 1H), 6.50 (d, J=7.8 Hz, 1H), 4.80 (td, J=7.7, 7.7, 5.4 Hz, 1H), 4.64-4.48 (m, 1H), 4.45-4.31 (m, 1H), 3.92 (dd, J=11.0, 3.9 Hz, 1H), 3.79-3.74 (m, 5H), 3.73-3.67 (m, 3H), 3.54 (dd, J=11.0, 6.7 Hz, 1H), 3.27 (d, J=4.9 Hz, 1H), 3.15-2.84 (m, 6H), 2.72 (dd, J=14.0, 7.8 Hz, 1H), 2.55-2.39 (m, 4H), 1.48 (s, 3H). MS (EI) for C31H40N4O8, found 597.1 (MH+).

Workup

  1. temperaturewas cooled to ambient temperature
  2. filtrationfiltered through Celite
  3. customPurification by column chromatography (3:1 DCM/ethyl acetate+0-10% methanol)

Sources & evidence

ORD record
ord-a09a69dece1e41d39af66558c628eee5
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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