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

HRID 1455596Notes

Reaction equation

HRID 1455596 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.FC(F)(F)C(O)=O.[NH2:50][CH:51]([CH2:62][CH3:63])[C@@H:52]([C:54]1[O:55][C:56]([CH:59]2[CH2:61][CH2:60]2)=[N:57][N:58]=1)[OH:53].[F:64][C:65]([F:83])([CH2:80][CH2:81][CH3:82])[CH2:66][C@H:67]([NH:71][C:72]([N:74]1[CH2:79][CH2:78][O:77][CH2:76][CH2:75]1)=[O:73])[C:68](O)=[O:69]>C(Cl)Cl>[CH:59]1([C:56]2[O:55][C:54]([CH:52]([OH:53])[C@@H:51]([NH:50][C:68]([C@@H:67]([NH:71][C:72]([N:74]3[CH2:79][CH2:78][O:77][CH2:76][CH2:75]3)=[O:73])[CH2:66][C:65]([F:83])([F:64])[CH2:80][CH2:81][CH3:82])=[O:69])[CH2:62][CH3:63])=[N:58][N:57]=2)[CH2:61][CH2:60]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 57535361(S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-heptanoic acidHCID 68822405HCID 68822405, compound

Product 1

HCID 86607347morpholine-4-carboxylic acid ((S)-1-{(S)-1-[(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-hydroxy-methyl]-propylcarbamoyl-}3,3-difluoro-hexyl)-amideYield 61.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

PyBOP (171.73 mg, 0.33 mmol), diisopropylethylamine (0.0575 mL, 0.33 mmol) and (S)-2-amino-1-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-butan-1-ol; compound with trifluoro-acetic acid (0.30 mmol) are added to a solution of (S)-4,4-Difluoro-2-[(morpholine-4-carbonyl)-amino]-heptanoic acid (88.29 mg, 0.30 mmol) in dry methylene chloride (4 mL) and the reaction mixture is stirred overnight at room temperature. The reaction is quenched with aqueous sodium bicarbonate, extracted twice with methylene chloride, the organic extracts are dried over sodium sulfate 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)-1-{(S)-1-[(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-hydroxy-methyl]-propylcarbamoyl-}3,3-difluoro-hexyl)-amide as a solid (87 mg). LC/MS 97%, 474 (M+1).

Workup

  1. customThe reaction is quenched with aqueous sodium bicarbonate
  2. extractionextracted twice with methylene chloride
  3. dry with materialthe organic extracts are dried over sodium sulfate
  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-c37ddc0678d342238d981b71640c1b0a
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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