HCID 66591106, compound → HCID 86637640, compound

HRID 538422Notes

Reaction equation

HRID 538422 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[O:5][C:6]=1[CH:7]1[CH2:12][CH:11]=[N:10][C:9]([Cl:13])=[N:8]1>CCOC(C)=O.O=[Mn]=O>[Br:1][C:2]1[N:3]=[C:4]([C:14]2[CH:15]=[CH:16][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=2)[O:5][C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([Cl:13])[N:8]=1

Participants

4

Reactant 1

HCID 66591106HCID 66591106, compound

Product 1

HCID 86637640HCID 86637640, compoundYield 27.3%

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of lithium diisopropylamide (1.8 M in THF-heptane-ethylbenzene, 1.4 mL, 2.6 mmol) was added dropwise into a cooled solution of 5-bromo-2-(4-(trifluoromethyl)phenyl)oxazole (620 mg, 2.1 mmol) in dry THF (20 mL) at −78° C. After 2.5 h, 2-chloropyrimidine (292 mg, 2.6 mmol) was added. After 10 min, the reaction flask was raised half way out of the acetone-dry ice bath and maintained for 30 min, after which the reaction was warmed to 10° C. in an ice-water bath and maintained for 1 h. The reaction was quenched with water (1 mL) and concentrated. The resulting mixture was partitioned between EtOAc (70 mL) and water (40 mL), and the layers were separated. The organic phase was washed with water, brine, dried (Na2SO4), and concentrated to give 859 mg of a residue as 4-bromo-5-(2-chloro-4,5-dihydropyrimidin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole which was used in the next step without further purification: LCMS (m/z): 407.9 (MH+), tR=0.83 min. A suspension of 4-bromo-5-(2-chloro-4,5-dihydropyrimidin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole (859 mg, 2.12 mmol) and MnO2 (1.8 g, 21.2 mmol) in EtOAc (10 mL) was irradiated at 110° C. for 10 min in a microwave reactor. The reaction was allowed to cool to rt and was filtered through a plastic membrane. The filtrate was concentrated and resulting residue was triturated with EtOAc to afford 234 mg of 4-bromo-5-(2-chloropyrimidin-4-yl)-2-(4-(trifluoromethyl)phenyl)oxazole: LCMS (m/z): 406.0 (MH+), tR=1.19 min.

Workup

  1. customwas used in the next step without further purification
  2. customwas irradiated at 110° C. for 10 min in a microwave reactor
  3. filtrationwas filtered through a plastic membrane
  4. concentrationThe filtrate was concentrated
  5. customresulting residue
  6. customwas triturated with EtOAc

Sources & evidence

ORD record
ord-774813e9063a48528b9983ac6c94fcf8
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Reaction notes

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