Diisopropylethylamine → morpholine-4-carboxylic acid ((R)-2-cyclopropylmethanesulfonyl-1-{(S)-1-[hydroxy-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-methyl]-propylcarbamoyl}-ethyl)-amide

HRID 489641Notes

Reaction equation

HRID 489641 reaction equation
C1(C2N=C(C(C(N[C:15]([CH:17]([NH:26][C:27]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[O:28])[CH2:18][S:19]([CH2:22][CH:23]([CH3:25])[CH3:24])(=[O:21])=[O:20])=[O:16])CC)=O)ON=2)CC1.FC(F)(F)C(O)=O.[NH2:42][CH:43]([CH2:55][CH3:56])[C@@H:44]([C:46]1[N:50]=[C:49]([C:51]([F:54])([F:53])[F:52])[O:48][N:47]=1)[OH:45].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH:23]1([CH2:22][S:19]([CH2:18][C@H:17]([NH:26][C:27]([N:29]2[CH2:30][CH2:31][O:32][CH2:33][CH2:34]2)=[O:28])[C:15](=[O:16])[NH:42][C@H:43]([CH:44]([OH:45])[C:46]2[N:50]=[C:49]([C:51]([F:54])([F:53])[F:52])[O:48][N:47]=2)[CH2:55][CH3:56])(=[O:20])=[O:21])[CH2:24][CH2:25]1

Participants

6

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 10239165Morpholine-4-carboxylic acid [1-[1-(3-cyclopropyl-1,2,4-oxadiazole-5-carbonyl)-propylcarbamoyl]-2-(2-methyl-propane-1-sulfonyl)-ethyl]-amideHCID 86588340(S)-2-amino-1-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-butan-1-ol trifluoroacetate

Product 1

HCID 86590023morpholine-4-carboxylic acid ((R)-2-cyclopropylmethanesulfonyl-1-{(S)-1-[hydroxy-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-methyl]-propylcarbamoyl}-ethyl)-amideYield 84.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (R)-3-cyclopropylmethanesulfonyl-2-[(morpholine-4-carbonyl)-amino]-propionic acid (266 mg, 0.83 mmol, Reference Example 4) in dimethylformamide (10 mL) was treated successively with (S)-2-amino-1-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-butan-1-ol trifluoroacetate (282 mg, 0.83 mmol, Reference Example 13), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (316 mg, 0.83 mmol) and diisopropylethylamine (0.289 mL, 1.66 mmol). Reaction stirred at room temperature overnight. Solvent evaporated under reduced pressure. Residue taken up in ethyl acetate and washed with 1N hydrochloric acid, saturated aqueous bicarbonate solution and water, dried over Na2SO4 and solvent evaporated under reduced pressure to give morpholine-4-carboxylic acid ((R)-2-cyclopropylmethanesulfonyl-1-{(S)-1-[hydroxy-(5-trifluoromethyl-1,2,4-oxadiazol-3-yl)-methyl]-propylcarbamoyl}-ethyl)-amide as a brown oil (370 mg). MS: 528 (MH+).

Workup

  1. customReaction
  2. customSolvent evaporated under reduced pressure
  3. washwashed with 1N hydrochloric acid, saturated aqueous bicarbonate solution and water
  4. dry with materialdried over Na2SO4 and solvent
  5. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-35aaf175acac428ca0831fbe51817aaf
Source dataset
uspto-grants-2005_12
Patent number
US06977256B2

Reaction notes

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