Diisopropylethylamine → morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-{hydroxy-[5-(4-trifluoromethoxy-phenyl)-1,3,4-oxadiazol-2-yl]-methyl)-propylcarbamoyl)-hexyl]-amide

HRID 1455598Notes

Reaction equation

HRID 1455598 reaction equation
C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH2:43][CH:44]([CH2:63][CH3:64])[C@@H:45]([C:47]1[O:48][C:49]([C:52]2[CH:57]=[CH:56][C:55]([O:58][C:59]([F:62])([F:61])[F:60])=[CH:54][CH:53]=2)=[N:50][N:51]=1)[OH:46].[F:65][C:66]([F:84])([CH2:81][CH2:82][CH3:83])[CH2:67][C@H:68]([NH:72][C:73]([N:75]1[CH2:80][CH2:79][O:78][CH2:77][CH2:76]1)=[O:74])[C:69](O)=[O:70]>C(Cl)Cl>[F:84][C:66]([F:65])([CH2:81][CH2:82][CH3:83])[CH2:67][C@H:68]([NH:72][C:73]([N:75]1[CH2:76][CH2:77][O:78][CH2:79][CH2:80]1)=[O:74])[C:69](=[O:70])[NH:43][C@H:44]([CH:45]([OH:46])[C:47]1[O:48][C:49]([C:52]2[CH:53]=[CH:54][C:55]([O:58][C:59]([F:61])([F:60])[F:62])=[CH:56][CH:57]=2)=[N:50][N:51]=1)[CH2:63][CH3:64]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 57535361(S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-heptanoic acidHCID 68823850(S)-2-Amino-1-[5-(4-trifluoromethoxy-phenyl)-1,3,4-oxadiazol-2-yl]-butan-1-ol

Product 1

HCID 86607348morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-{hydroxy-[5-(4-trifluoromethoxy-phenyl)-1,3,4-oxadiazol-2-yl]-methyl)-propylcarbamoyl)-hexyl]-amideYield 85.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

PyBOP (68.69 mg, 0.13 mmol), diisopropylethylamine (0.023 mL, 0.13 mmol) and (S)-2-Amino-1-[5-(4-trifluoromethoxy-phenyl)-1,3,4-oxadiazol-2-yl]-butan-1-ol (38.0 mg, 0.12 mmol) are added to a solution of (S)-4,4-Difluoro-2-[(morpholine-4-carbonyl)-amino]-heptanoic acid (34 mg, 0.12 mmol) in dry methylene chloride (4 mL) and the reaction mixture is stirred overnight at room temperature. The reaction is quenched with aqueous NaHCO3, extracted twice with methylene chloride, the organic extracts are dried over Na2SO4 and evaporated under reduced pressure. Column chromatography on silica eluting with a mixture of methylene chloride and ethyl acetate gives morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-{hydroxy-[5-(4-trifluoromethoxy-phenyl)-1,3,4-oxadiazol-2-yl]-methyl}-propylcarbamoyl)-hexyl]-amide as a solid (61 mg). LC/MS 71%, M+1=594

Workup

  1. customThe reaction is quenched with aqueous NaHCO3
  2. extractionextracted twice with methylene chloride
  3. dry with materialthe organic extracts are dried over Na2SO4
  4. customevaporated under reduced pressure
  5. additionColumn chromatography on silica eluting with a mixture of methylene chloride and ethyl acetate

Sources & evidence

ORD record
ord-e89b73ad05ab4ac5b9ff363e21eb7125
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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