Dichloromethane → 2,5-Dichloro-4-(6-fluoropyridin-2-yl)pyrimidine

HRID 1623271Notes

Reaction equation

HRID 1623271 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([Cl:9])=[CH:4][N:3]=1.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[N:12]=1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[Cl:1][C:2]1[N:7]=[C:6]([C:13]2[CH:14]=[CH:15][CH:16]=[C:11]([F:10])[N:12]=2)[C:5]([Cl:9])=[CH:4][N:3]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 2372592,4,5-TrichloropyrimidineHCID 426145762-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Product 1

HCID 866506062,5-Dichloro-4-(6-fluoropyridin-2-yl)pyrimidineYield 72.3%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2,4,5-trichloropyrimidine (49.3 mg, 0.269 mmol), 2-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (50 mg, 0.224 mmol), PdCl2(dppf).CH2Cl2 adduct (18.31 mg, 0.022 mmol), DME (0.7 ml), and 2M sodium carbonate (0.247 ml, 0.493 mmol) reaction mixture was stirred at about 80° C. until the reaction mixture was complete, as indicated by LCMS. The reaction mixture was cooled, diluted with 5 ml of ethyl acetate and 1 ml of methanol, filtered and concentrated to yield a crude solid. The crude material was purified by silica gel chromatography using a 12 g column, eluting from 0%-40% ethyl acetate with hexane. The desired fractions were concentrated to constant mass, to yield 39.5 mg of titled compound as a free base. LCMS (m/z): 244.0 (MH+), retention time=0.89 min.

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customto yield a crude solid
  5. customThe crude material was purified by silica gel chromatography
  6. washeluting from 0%-40% ethyl acetate with hexane
  7. concentrationThe desired fractions were concentrated to constant mass

Sources & evidence

ORD record
ord-0c060a95a65040b5a10b058dcf168471
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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