Diisopropylethylamine → Ethyl 6-{[2-cyclopentyl-2-{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-yl)methyl]-phenyl}acetyl]amino}-2-methylhexanoate

HRID 238186Notes

Reaction equation

HRID 238186 reaction equation
CCN(C(C)C)C(C)C.[CH:10]1([CH:15]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][N:26]3[C:31](=[O:32])[CH2:30][O:29][C:28]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[N:27]3)=[CH:21][CH:20]=2)[C:16](O)=[O:17])[CH2:14][CH2:13][CH2:12][CH2:11]1.[NH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH:44]([CH3:50])[C:45]([O:47][CH2:48][CH3:49])=[O:46].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH:10]1([CH:15]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][N:26]3[C:31](=[O:32])[CH2:30][O:29][C:28]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[N:27]3)=[CH:21][CH:20]=2)[C:16]([NH:39][CH2:40][CH2:41][CH2:42][CH2:43][CH:44]([CH3:50])[C:45]([O:47][CH2:48][CH3:49])=[O:46])=[O:17])[CH2:14][CH2:13][CH2:12][CH2:11]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 58074500Ethyl 6-amino-2-methylhexanoateHCID 58074507cyclopentyl{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-yl)methyl]phenyl}acetic acid

Product 1

HCID 58074503Ethyl 6-{[2-cyclopentyl-2-{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-yl)methyl]-phenyl}acetyl]amino}-2-methylhexanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

At RT, 72 μl (0.415 mmol) of DIEA were added to a solution of 148 mg (0.377 mmol) of (+)-cyclopentyl{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-yl)methyl]phenyl}acetic acid and 98 mg (about 0.66 mmol, crude material) of ethyl 6-amino-2-methylhexanoate in 1.0 ml of DMF. The resulting mixture was cooled to 0° C., and four portions of altogether 186.4 mg (0.49 mmol) of HATU were then added. The reaction mixture was slowly warmed to RT, stirred at RT for 16 h and then added to water and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. Purification of the residue by preparative RP-HPLC (acetonitrile/water gradient) gave 134.0 mg (64.9% of theory) of the target compound as a diastereomer mixture.

Workup

  1. temperatureThe reaction mixture was slowly warmed to RT
  2. extractionextracted three times with ethyl acetate
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customPurification of the residue by preparative RP-HPLC (acetonitrile/water gradient)
  6. customgave 134.0 mg (64.9% of theory) of the target compound as a diastereomer mixture

Sources & evidence

ORD record
ord-c1f39699d93e477a93dda1afdf1fc082
Source dataset
uspto-grants-2014_02
Patent number
US08642592B2

Reaction notes

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