Triethylamine → HCID 53973617, compound

HRID 849854Notes

Reaction equation

HRID 849854 reaction equation
[CH3:1][NH:2][C@@H:3]([C:11]1[O:15][C:14]([C:16]([NH2:18])=[O:17])=[N:13][N:12]=1)[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(OC([CH2:26][NH:27][C@H:28]([CH2:32][C:33]1[CH:42]=[CH:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:34]=1)[C:29]([OH:31])=O)=O)(C)(C)C.ON1C2N=C[CH:51]=[CH:52][C:47]=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH2:65](N(CC)CC)C.[C:72]([O:75]CC)(=[O:74])C>ClCCl.CN(C=O)C.O>[C:52]([O:75][C:72](=[O:74])[N:27]([C@@H:28]([C:29](=[O:31])[N:2]([C@@H:3]([C:11]1[O:15][C:14]([C:16](=[O:17])[NH2:18])=[N:13][N:12]=1)[CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)[CH3:1])[CH2:32][C:33]1[CH:42]=[CH:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:34]=1)[CH3:26])([CH3:51])([CH3:47])[CH3:65]

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 53913605HCID 53913605, compoundHCID 54532855HCID 54532855, compound

Product 1

HCID 53973617HCID 53973617, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

5-((1R)-1-Methylamino-2-phenylethyl)-[1,3,4]oxadiazole-2-carboxylic acid amide (240 mg, 0.98 mmol), (R)-2-((tert-butoxycarbonyl)methylamino)-3-(2-naphthyl)propionic acid (320 mg, 0.98 mmol) and 1-hydroxy-7-azabenzotriazole (133 mg, 0.98 mmol) were dissolved in dichloromethane (8 ml) and DMF (4 ml). The solution was cooled to 0° C. and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (230 mg, 1.18 mmol) was added. After 10 min triethylamine (0.35 ml, 2.46 mmol) was added. The solution was stirred for 1 h at 0° C. and subsequently for 16 h at room temp. The solution was diluted with ethyl acetate (30 ml) and water (20 ml). The phases were separated and the aqueous phase was extracted with ethyl acetate (20 ml). The combined organic layers were washed with a saturated solution of sodium hydrogencarbonate (30 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (50 g) with ethyl acetate to give 301 mg of ((1R)-1-(((1R)-1-(5-carbamoyl-[1,3,4]oxadiazol-2-yl)-2-phenylethyl)methylcarbamoyl)-2-(2-naphthyl)ethyl)methylcarbamic acid tert-butylester.

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with ethyl acetate (20 ml)
  3. washThe combined organic layers were washed with a saturated solution of sodium hydrogencarbonate (30 ml)
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customThe crude product was purified by flash chromatography on silica (50 g) with ethyl acetate

Sources & evidence

ORD record
ord-af906280f9e943d392048324366b1a01
Source dataset
uspto-grants-2000_01
Patent number
US06013658

Reaction notes

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