Morpholine → 2-(2,6-Difluorophenyl)-5-(4-(morpholine-4-carbonyl)phenylamino)oxazole-4-carbonitrile

HRID 715011Notes

Reaction equation

HRID 715011 reaction equation
[C:1]([C:3]1[N:4]=[C:5]([C:18]2[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=2[F:25])[O:6][C:7]=1[NH:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=1)#[N:2].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.[NH:59]1[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1>CCOC(C)=O>[F:25][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]([F:24])[C:18]=1[C:5]1[O:6][C:7]([NH:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([N:59]3[CH2:64][CH2:63][O:62][CH2:61][CH2:60]3)=[O:15])=[CH:11][CH:10]=2)=[C:3]([C:1]#[N:2])[N:4]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595874924-(4-Cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)benzoic acid

Product 1

HCID 595875572-(2,6-Difluorophenyl)-5-(4-(morpholine-4-carbonyl)phenylamino)oxazole-4-carbonitrileYield 37.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)benzoic acid (0.020 g, 0.059 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.022 g, 0.059 mmol), and diisopropylethylamine (0.020 mL, 0.117 mmol) in N,N-dimethylformide (2 mL) was added morpholine (0.005 mL, 0.059 mmol) and the reaction mixture stirred at room temperature for 16 hours. The reaction was then diluted with EtOAc washed with 1M HCl, water and brine. The organic phase was dried over MgSO4 and the solvent removed in vacuo. The residue was purified by preparative HPLC to afford 2-(2,6-difluorophenyl)-5-(4-(morpholine-4-carbonyl)phenylamino)oxazole-4-carbonitrile (0.009 g, 0.022 mmol, 37%) as a yellow solid. LCMS (2) Rt: 2.38 min; m/z (ES+) 411.

Workup

  1. washwashed with 1M HCl, water and brine
  2. dry with materialThe organic phase was dried over MgSO4
  3. customthe solvent removed in vacuo
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-cc54645a46364bb1bda6c15df23d7c7a
Source dataset
uspto-grants-2015_11
Patent number
US09187465B2

Reaction notes

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