1-Hydroxybenzotriazole → Tert-Butyl 6-{[2-cyclopentyl-2-{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-yl)-methyl]phenyl}acetyl]amino}heptanoate

HRID 238185Notes

Reaction equation

HRID 238185 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]2N(O)N=N[C:5]=2[CH:6]=1.CCN(C(C)C)C(C)C.[CH:20]1([CH:25]([C:29]2[CH:34]=[CH:33][C:32]([CH2:35][N:36]3[C:41](=[O:42])[CH2:40][O:39][C:38](C4C=CC=CC=4)=[N:37]3)=[CH:31][CH:30]=2)[C:26]([OH:28])=O)[CH2:24][CH2:23][CH2:22][CH2:21]1.[NH2:49][CH:50]([CH3:62])[CH2:51][CH2:52][CH2:53][CH2:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[CH:20]1([CH:25]([C:29]2[CH:30]=[CH:31][C:32]([CH2:35][N:36]3[C:41](=[O:42])[CH2:40][O:39][C:38]([C:5]4[CH:4]=[CH:3][CH:2]=[CH:1][CH:6]=4)=[N:37]3)=[CH:33][CH:34]=2)[C:26]([NH:49][CH:50]([CH3:62])[CH2:51][CH2:52][CH2:53][CH2:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])=[O:28])[CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 13997370Tert-butyl 6-aminoheptanoateHCID 58074507cyclopentyl{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-yl)methyl]phenyl}acetic acid

Product 1

HCID 58074539Tert-Butyl 6-{[2-cyclopentyl-2-{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-yl)-methyl]phenyl}acetyl]amino}heptanoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

At RT, 41.3 mg (0.306 mmol) of HOBt and 126 μl (0.764 mmol) of DIEA were added to a solution of 100 mg (0.255 mmol) of (+)-cyclopentyl{4-[(5-oxo-2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazin-4-yl)methyl]phenyl}acetic acid and 76.9 mg (0.382 mmol) of tert-butyl(+/−)-6-aminoheptanoate in 0.3 ml of DMF. The resulting mixture was cooled to 0° C., after which 116.3 mg (0.306 mmol) of HATU were added. The reaction mixture was slowly warmed to RT, stirred at RT for 1 h and then diluted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution and with saturated sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative RP-HPLC (acetonitrile/water gradient). This gave 118 mg (about 83% pure, about 67% of theory) of the target compound as a diastereomer mixture.

Workup

  1. temperatureThe reaction mixture was slowly warmed to RT
  2. washThe organic phase was washed with saturated sodium bicarbonate solution and with saturated sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative RP-HPLC (acetonitrile/water gradient)

Sources & evidence

ORD record
ord-4b9e794f2e9e4f5c9f4019ec50ee243d
Source dataset
uspto-grants-2014_02
Patent number
US08642592B2

Reaction notes

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