Diisopropylethylamine → HCID 117607891, compound

HRID 58909Notes

Reaction equation

HRID 58909 reaction equation
OC(C(F)(F)F)=O.[NH2:8][C@@H:9]([CH3:35])[C:10]([NH:12][C@@H:13]([CH2:31][CH:32]1[CH2:34][CH2:33]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:36]1[CH2:41][CH2:40][N:39]([CH2:42][C:43](O)=[O:44])[CH2:38][CH2:37]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>[CH:32]1([CH2:31][C@H:13]([NH:12][C:10](=[O:11])[C@@H:9]([NH:8][C:43](=[O:44])[CH2:42][N:39]2[CH2:40][CH2:41][O:36][CH2:37][CH2:38]2)[CH3:35])[C:14]([NH:16][C@@H:17]([CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:18]([C@@:20]2([CH3:23])[CH2:22][O:21]2)=[O:19])=[O:15])[CH2:34][CH2:33]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 131737028HCID 131737028, compound

Product 1

HCID 117607891HCID 117607891, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To (S)-2-((S)-2-aminopropanamido)-3-cyclopropyl-N-((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)propanamide TFA salt (377 mg, 0.779 mmol) was added 2-morpholinoacetic acid (226 mg, 1.56 mmol), HATU (622 mg, 1.64 mmol), and DMF (4 mL). The mixture was cooled to 0° C. and DIEA (0.68 mL, 3.9 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-cyclopropyl-N-((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanamide (320 mg, 80%) as a colorless solid. 1H NMR (400 MHz, CDCl3): δ 7.54 (d, J=7.6 Hz, 1H), 7.32-7.22 (m, 3H), 7.16-7.14 (m, 2H), 6.67 (d, J=7.6 Hz, 1H), 6.47 (d, J=7.6 Hz, 1H), 4.86-4.81 (m, 1H), 4.43 (q, J=6.8 Hz, 2H), 4.34 (dd, J=14.4, 6.8 Hz, 1H), 3.74-3.72 (m, 4H), 3.30 (d, J=4.8 Hz, 1H), 3.14 (dd, J=14.0, 5.2 Hz, 1H), 3.04 (d, J=4.8 Hz, 2H), 2.92 (d, J=4.8 Hz, 1H), 2.83 (dd, J=14.0, 7.8 Hz, 1H), 2.54-2.52 (m, 4H), 1.56 (t, J=6.8 Hz, 2H), 1.50 (s, 3H), 1.35 (d, J=7.2 Hz, 3H), 0.41-0.36 (m, 2H), 0.05-0.00 (m, 2H). MS (EI) for C27H38N4O6, found 515.4 (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-be942a33e4e44c9eaf242be2b8a00589
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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