Dimethylformamide → HCID 56654397, compound

HRID 1961543Notes

Reaction equation

HRID 1961543 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[C:20]([Cl:24])=[C:19]([Cl:25])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[C:26]1([F:35])[CH2:29][N:28]([C:30]([CH:32]2[CH2:34][CH2:33]2)=[O:31])[CH2:27]1.[CH3:36][N:37](C=O)C>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:32]1([C:30]([N:28]2[CH2:29][C:26]([C:3]3[CH:4]=[CH:5][C:6]([C:8]4[CH2:12][C:11]([C:17]5[CH:22]=[C:21]([Cl:23])[C:20]([Cl:24])=[C:19]([Cl:25])[CH:18]=5)([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=4)=[CH:7][C:2]=3[C:36]#[N:37])([F:35])[CH2:27]2)=[O:31])[CH2:33][CH2:34]1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 56655093HCID 56655093, compound

Product 1

HCID 56654397HCID 56654397, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (3-(2-bromo-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)-3-fluoroazetidin-1-yl)(cyclopropyl)methanone (Example 83, 35 mg, 0.06 mmol) in DMF was added ZnCN (15 mg, 0.12 mmol) and the reaction was degassed with N2 purge. Pd(PPh3)4 (4 mg, 0.003 mmol) was added and the reaction mixture was heated under microwave irradiation at 150° C. for 15 minutes. Next, the reaction mixture was diluted with water and extracted with EtOAc (75 mL). The organic phase was dried (Na2SO4) and concentrated under vacuum. Crude product was chromatographed (12 g Redi-Sep column) eluting from 100% heptane to 60:40 EtOAc:heptane to afford the final product (18 mg, 56%) as a solid. 1H NMR (CDCl3) δ ppm: 8.08 (1H), 8.00 (1H), 7.70 (1H), 7.66 (2H), 4.98-4.52 (4H), 4.12 (1H), 3.73 (1H), 1.49 (1H), 1.10-0.81 (4H); m/z (Cl) 560 ([M+H]+.

Workup

  1. customthe reaction was degassed with N2
  2. custompurge
  3. extractionextracted with EtOAc (75 mL)
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. concentrationconcentrated under vacuum
  6. customCrude product was chromatographed (12 g Redi-Sep column)
  7. washeluting from 100% heptane to 60:40 EtOAc

Sources & evidence

ORD record
ord-c4cb678c86744e21b42450ca77c9cac9
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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