Diisopropylethylamine → {3-(3-Amino-1,2,4-oxadiazol-5-yl)-5-[4-(trifluoromethyl)phenyl]piperidin-1-yl}(morpholin-4-yl)methanone

HRID 661207Notes

Reaction equation

HRID 661207 reaction equation
[N:1]1([C:7]([N:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[CH2:12][CH:11]([C:25]([OH:27])=O)[CH2:10]2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.O.S(O)(O)(=O)=O.O[NH:77][C:78]([NH2:80])=[NH:79].ONC(N)=N>CN(C=O)C>[NH2:80][C:78]1[N:79]=[C:25]([CH:11]2[CH2:12][CH:13]([C:15]3[CH:16]=[CH:17][C:18]([C:21]([F:22])([F:24])[F:23])=[CH:19][CH:20]=3)[CH2:14][N:9]([C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[O:8])[CH2:10]2)[O:27][N:77]=1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 2724699PyBOPHCID 580024471-(Morpholin-4-ylcarbonyl)-5-[4-(trifluoromethyl)phenyl]piperidine-3-carboxylic acidHCID 178513195HCID 178513195, compound

Product 1

HCID 58116494{3-(3-Amino-1,2,4-oxadiazol-5-yl)-5-[4-(trifluoromethyl)phenyl]piperidin-1-yl}(morpholin-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under argon, a solution of 11.9 g (30.7 mmol) of carboxylic acid from Example 4A in 150 ml of DMF was admixed at RT with 19.2 g (36.8 mmol) of PYBOP and 10.7 ml (61.4 mmol) of N,N′-diisopropylethylamine. Subsequently, the mixture was stirred at RT for 30 min and then the solution was added dropwise within 1.5 h to a suspension of 24.5 g (92.1 mmol) of hydroxyguanidine hemisulphate hemihydrate, 16.1 ml (92.1 mmol) of N,N′-diisopropylethylamine and 4 Å molecular sieve. The reaction mixture was stirred at RT for 1 h and then filtered through a frit. The residue was washed with 200 ml of DMF and then the combined organic phases were stirred at 130° C. (preheated oil bath) for 1.5 h. Subsequently, the solvent was removed under reduced pressure and the residue was admixed with 300 ml of diethyl ether and 300 ml of 1 N aqueous sodium hydroxide solution, and stirred vigorously for 24 h. The solid formed was filtered off, washed with water and diethyl ether and then dried under high vacuum. Yield: 8.80 g (66% of theory)

Workup

  1. stirringThe reaction mixture was stirred at RT for 1 h
  2. filtrationfiltered through a frit
  3. washThe residue was washed with 200 ml of DMF
  4. stirringthe combined organic phases were stirred at 130° C. (preheated oil bath) for 1.5 h
  5. customSubsequently, the solvent was removed under reduced pressure
  6. stirringstirred vigorously for 24 h
  7. customThe solid formed
  8. filtrationwas filtered off
  9. washwashed with water and diethyl ether
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-9b66fcc9003b479da47776a344370ae8
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

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