Sodium Carbonate → HCID 59633032, compound

HRID 2369088Notes

Reaction equation

HRID 2369088 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:11]([C:12]3[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=3)[N:10]=[C:9]([C:18]([O:20][CH3:21])=[O:19])[CH:8]=2)=[CH:4][CH:3]=1.[CH3:22][S:23]([C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)(=[O:25])=[O:24].C([O-])([O-])=O.[Na+].[Na+].C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.[Pd].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>[CH3:22][S:23]([C:26]1[CH:31]=[C:30]([C:2]2[S:6][C:5]([C:7]3[N:11]([C:12]4[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=4)[N:10]=[C:9]([C:18]([O:20][CH3:21])=[O:19])[CH:8]=3)=[CH:4][CH:3]=2)[CH:29]=[CH:28][CH:27]=1)(=[O:25])=[O:24]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 13097Triphenylphosphine OxideHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 59631818HCID 59631818, compound2×

Product 1

HCID 59633032HCID 59633032, compoundYield 24%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of methyl 5-(5-bromothiophen-2-yl)-1-(pyridin-4-yl)-1H-pyrazole-3-carboxylate (480 mg, 1.3 mmol) and 3-(methylsulfonyl)phenylboronic acid (390 mg, 1.9 mmol) was suspended in THF (6 mL) with Na2CO3 (1.0 mL of a 2M aqueous solution, 2.0 mmol). The mixture was sparged with nitrogen for ˜10 minutes, treated with Pd(PPh3)4 (54 mg, 47 mol), and heated to 65° C. After 4 hours at 65° C. there was still starting methyl 5-(5-bromothiophen-2-yl)-1-(pyridin-4-yl)-1H-pyrazole-3-carboxylate visible as evidenced by LC/MS. Additional palladium catalyst was added and heating was continued. After heating at 65° C. overnight the reaction mixture was concentrated under reduced pressure to afford a dark semi-solid that was triturated with EtOAc and filtered to remove the solids. The filtrate was concentrated under reduced pressure and purified by flash column chromatography eluting with a gradient from 0% to 50% MeCN/CH2Cl2 to afford methyl 5-(5-(3-(methylsulfonyl)phenyl)-thiophen-2-yl)-1-(pyridin-4-yl)-1H-pyrazole-3-carboxylate (137 mg, 24% yield) as a mixture with triphenylphosphine oxide. This colorless film will be carried on to the Grignard addition without further purification.

Workup

  1. customThe mixture was sparged with nitrogen for ˜10 minutes
  2. temperatureheating
  3. temperatureAfter heating at 65° C. overnight the reaction mixture
  4. concentrationwas concentrated under reduced pressure
  5. customto afford a dark semi-solid
  6. customthat was triturated with EtOAc
  7. filtrationfiltered
  8. customto remove the solids
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. custompurified by flash column chromatography
  11. washeluting with a gradient from 0% to 50% MeCN/CH2Cl2

Sources & evidence

ORD record
ord-1046c9f5fdbb4708b5471f0cb9f7283e
Source dataset
uspto-grants-2014_04
Patent number
US08703805B2

Reaction notes

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