4-Methylmorpholine → (3-(2-chloro-6-fluorophenyl)-5-(1-(3-chlorophenyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)isoxazol-4-yl)(morpholino)methanone

HRID 2047239Notes

Reaction equation

HRID 2047239 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:13]([C:14]([OH:16])=O)=[C:12]([C:17]2[CH:18]=[N:19][N:20]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[C:21]=2[C:22]([F:25])([F:24])[F:23])[O:11][N:10]=1.[NH:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CN1CCOCC1>CN(C=O)C.CN1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:13]([C:14]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[O:16])=[C:12]([C:17]2[CH:18]=[N:19][N:20]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[C:21]=2[C:22]([F:24])([F:23])[F:25])[O:11][N:10]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 8083Morpholine2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 757711-Hydroxybenzotriazole2×HCID 86668506HCID 86668506, compound

Product 1

HCID 86668507(3-(2-chloro-6-fluorophenyl)-5-(1-(3-chlorophenyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)isoxazol-4-yl)(morpholino)methanoneYield 46,820.801%

Reagents, catalysts & solvents 2

HCID 79724-MethylmorpholineCatalystHCID 6228DimethylformamideSolvent

Procedure

3-(2-chloro-6-fluorophenyl)-5-(1-(3-chlorophenyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)isoxazole-4-carboxylic acid (50 mg, 0.0001 mmol), Morpholine (9 mg, 0.0001 mmol), HOBt (14 mg, 0.0001 mmol) and EDCI (19 mg 0.00012 mmol) were dissolved in 1 mL dry DMF. N-Methylmorpholine (100 NL, 0.001 mmol) was added and the reaction mixture was stirred at room temperature overnight. Morpholine, HOBt, EDCI and N-Methylmorpholine were added again in the aforementioned ratios. The mixture was stirred at room temperature for 24 h. DMF was removed by evaporation. An aqueous solution of 5% citric acid was added. The precipitate was filtered and dried. The product (example B-35) was purified by pTLC (PE/EE 5/5) to give 26 mg of a yellow oil (yield 45%). Result of LC/MS MH+: 554.7; 1H NMR (CDCl3): 8.15 (1H, s, CH-pyraz.), 7.35-7.6 (6H, m, CH-arom), 7.15 (1H, t, CH-arom), 3.6 (4H, m, CH2-morpholine), 3.18 (4H, m, CH2-morpholine).

Workup

  1. stirringThe mixture was stirred at room temperature for 24 h
  2. customDMF was removed by evaporation
  3. additionAn aqueous solution of 5% citric acid was added
  4. filtrationThe precipitate was filtered
  5. customdried

Sources & evidence

ORD record
ord-b34b0fc6735e4dd092233710ae339a26
Source dataset
uspto-grants-2013_11
Patent number
US08592456B2

Reaction notes

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