Cesium fluoride → HCID 118020586, compound

HRID 1777400Notes

Reaction equation

HRID 1777400 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[CH:11][N:10]([CH2:13][CH:14]3[N:19]([C:20]([C:22]4[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][C:23]=4I)=[O:21])[CH2:18][CH2:17][CH2:16][O:15]3)[N:9]=2)=[CH:4][CH:3]=1.C([Sn]([C:43]1[N:48]=[CH:47][CH:46]=[CH:45][N:44]=1)(CCCC)CCCC)CCC.[F-].[Cs+].[F-].[K+]>C1(C)C=CC=CC=1.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.[Cu](I)I>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[CH:11][N:10]([CH2:13][CH:14]3[N:19]([C:20]([C:22]4[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][C:23]=4[C:43]4[N:48]=[CH:47][CH:46]=[CH:45][N:44]=4)=[O:21])[CH2:18][CH2:17][CH2:16][O:15]3)[N:9]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 522689Potassium FluorideHCID 27632512-(Tributylstannyl)pyrimidineHCID 118020628HCID 118020628, compound

Product 1

HCID 118020586HCID 118020586, compound

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of (±)-(2-{[3-(4-fluorophenyl)-1H-pyrazol-1-yl]methyl}-1,3-oxazinan-3-yl)(2-iodo-5-methylphenyl)methanone obtained in Reference Example 23 (0.19 g, 0.38 mmol) and (tributylstannanyl)pyrimidine (0.15 mL, 0.46 mmol) in toluene (4 mL), Pd(PPh3)4 (0.044 g, 0.04 mmol), copper iodide (0.0070 g, 0.040 mmol) and cesium fluoride (0.12 g, 0.76 mmol) were added, and the resulting mixture was stirred with heating for 0.5 hours at 130° C. under irradiation of microwave. An aqueous solution of potassium fluoride was added to the reaction mixture, followed by extraction with CHCl3. The organic layer was washed with an aqueous solution of potassium fluoride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over Na2SO4, the drying agent was filtered off, and then concentrated under reduced pressure. The obtained residue was purified by column chromatography (HP-Sil 10 g, hexane/EtOAc=80/20 to 0/100) (KP-NH 12 g, hexane/EtOAc=80/20 to 0/100) to obtain the racemic mixture of title compound (0.099 g) (colorless oil). The obtained racemic mixture was divided using a semi-preparative column based on the racemic compound analysis conditions described earlier (condition 4, Rt1=3.9 min, Rt2=13.7 min) to obtain the title compound (0.036 g) having a short relative retention time (Rt1=3.9 min) (colorless oil).

Workup

  1. additionwere added
  2. extractionfollowed by extraction with CHCl3
  3. washThe organic layer was washed with an aqueous solution of potassium fluoride, water
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationthe drying agent was filtered off
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by column chromatography (HP-Sil 10 g, hexane/EtOAc=80/20 to 0/100) (KP-NH 12 g, hexane/EtOAc=80/20 to 0/100)
  8. customto obtain

Sources & evidence

ORD record
ord-562f5d7b45004656a7391f64abb7fbad
Source dataset
uspto-grants-2016_02
Patent number
US09266870B2

Reaction notes

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