Diisopropylethylamine → HCID 117607964, compound

HRID 58921Notes

Reaction equation

HRID 58921 reaction equation
OC(C(F)(F)F)=O.[NH2:8][C@@H:9]([CH2:40][O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:10]([NH:12][C@@H:13]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=1)[C:14]([NH:16][C@@H:17]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:18]([C@@:20]1([CH3:23])[CH2:22][O:21]1)=[O:19])=[O:15])=[O:11].[O:49]1[CH2:54][CH2:53][N:52]([CH2:55][C:56](O)=[O:57])[CH2:51][CH2:50]1.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>[CH2:42]([O:41][CH2:40][C@H:9]([NH:8][C:56](=[O:57])[CH2:55][N:52]1[CH2:53][CH2:54][O:49][CH2:50][CH2:51]1)[C:10]([NH:12][C@@H:13]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=1)[C:14]([NH:16][C@@H:17]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:18]([C@@:20]1([CH3:23])[CH2:22][O:21]1)=[O:19])=[O:15])=[O:11])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 4389684-Morpholineacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131737035HCID 131737035, compound

Product 1

HCID 117607964HCID 117607964, compoundYield 32.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To (S)-2-amino-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)propanamide TFA salt (2.94 mmol assumed) was added 2-morpholinoacetic acid (647 mg, 4.46 mmol), HATU (1.86 g, 4.91 mmol), and DMF (5 mL). The mixture was cooled to 0° C. and DIEA (3.10 mL, 17.8 mmol) was added. The reaction mixture was stirred at ambient temperature for 30 min then quenched with sodium bicarbonate (sat.), extracted with ethyl acetate (2×), dried with sodium sulfate, filtered, and concentrated. Purification by column chromatography (3:1 DCM/ethyl acetate+0-10% methanol) provided (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 (660 mg, 28% over 5 steps) as an amorphous colorless solid. MS (EI) for C38H46N4O8, found 687.4 (MH+).

Workup

  1. customthen quenched with sodium bicarbonate (sat.)
  2. extractionextracted with ethyl acetate (2×)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by column chromatography (3:1 DCM/ethyl acetate+0-10% methanol)

Sources & evidence

ORD record
ord-2fdf70258415441493a6b295bf222144
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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