Diisopropylethylamine → HCID 117607901, compound

HRID 58806Notes

Reaction equation

HRID 58806 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([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:4]=1.[NH2:29][C@@H:30]([CH2:37][C:38]1[CH2:42][CH2:41][CH2:40][CH: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>C(Cl)Cl.O>[C: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[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)[CH3:17])[CH2:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C:31]([C@@:33]2([CH3:36])[CH2:35][O:34]2)=[O:32])[CH2:42][CH2:41][CH2:40][CH:39]=1

Participants

7

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 68247340(S)-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanoic acidHCID 117607719HCID 117607719, compound

Product 1

HCID 117607901HCID 117607901, compoundYield 43.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanoic acid (850 mg, crude) and (S)-2-amino-3-(cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)propan-1-one (TFA salt, 200 mg, 0.680 mmol) in DCM (10 mL) was added HATU (283 mg, 0.750 mmol). The mixture was cooled to 0° C. and basified with DIEA to pH=8. The reaction mixture was stirred at ambient temperature for 30 min and water (30 mL) was added. The resulting mixture was extracted with DCM (30 mL×2) and the extracts were combined, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=2:1 to 1:2, then DCM/methanol=70:1) to afford (S)-N-((S)-3-(cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanamide (170 mg, 18%) as a colorless solid. 1H NMR (300 MHz, CDCl3): δ7.29 (br. s, 1H), 7.16 (d, J=8.7 Hz, 2H), 6.83 (d, J=8.7 Hz, 2H), 6.74 (d, J=7.2 Hz, 1H), 6.10 (d, J=7.2 Hz, 1H), 5.33 (s, 1H), 4.56-4.44 (m, 2H), 3.80 (s, 3H), 3.75-3.73 (m, 4H), 3.29 (d, J=4.8 Hz, 1H), 3.00-2.91 (m, 5H), 2.53-2.47 (m, 5H), 2.27-2.16 (m, 5H), 1.90-1.81 (m, 1H), 1.73 (s, 3H), 1.37 (d, J=7.2 Hz, 3H). MS (EI) for C30H42N4O7, found 571.4 (MH)+.

Workup

  1. extractionThe resulting mixture was extracted with DCM (30 mL×2)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=2:1 to 1:2

Sources & evidence

ORD record
ord-7733b4246dbc491f889e7731f996987e
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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