Sodium Carbonate → Methyl-4-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-5-methylthiophene-2-carboxylate

HRID 1842600Notes

Reaction equation

HRID 1842600 reaction equation
O1CCOCC1.Br[C:8]1[CH:9]=[N:10][N:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[N:13][C:12]=12.[CH3:18][O:19][C:20]([C:22]1[S:23][C:24]([CH3:36])=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:26]=1)=[O:21].C(=O)([O-])[O-].[Na+].[Na+]>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.O>[CH3:18][O:19][C:20]([C:22]1[S:23][C:24]([CH3:36])=[C:25]([C:8]2[CH:9]=[N:10][N:11]3[CH:16]=[C:15]([Cl:17])[CH:14]=[N:13][C:12]=23)[CH:26]=1)=[O:21]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 46703107Methyl 5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylateHCID 673469363-Bromo-6-chloropyrazolo[1,5-a]pyrimidine

Product 1

HCID 67348535Methyl-4-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-5-methylthiophene-2-carboxylateYield 67.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a flask containing 1,4-dioxane (58.1 mL) and water (19.4 mL) was added 3-bromo-6-chloropyrazolo[1,5-a]pyrimidine (3.60 g, 15.5 mmol), methyl-5-methyl-4-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)-thiophene-2-carboxylate (4.37 g, 15.5 mmol), palladium tetrakis (895 mg, 0.774 mmol), and sodium carbonate (4.92 g, 46.5 mmol). The reaction mixture was sealed and degassed with N2 for 15 min. The reaction mixture was then heated to 100° C. for 2 h. The reaction was cooled to room temperature and partitioned between water and ethyl acetate. The organic layer was dried with sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (dichloromethane:hexane:ethyl acetate 20:75:5 to 20:60:20) to afford the title compound (3.23 g, 10.5 mmol). LRMS (APCI) calc'd for (C13H10ClN3O2S) [M+H]+, 308.0; found 308.0.

Workup

  1. customThe reaction mixture was sealed
  2. customdegassed with N2 for 15 min
  3. temperatureThe reaction was cooled to room temperature
  4. custompartitioned between water and ethyl acetate
  5. dry with materialThe organic layer was dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by column chromatography (dichloromethane:hexane:ethyl acetate 20:75:5 to 20:60:20)

Sources & evidence

ORD record
ord-90be0aec3c08480d97191f115ef8f4e4
Source dataset
uspto-grants-2015_02
Patent number
US08946237B2

Reaction notes

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