Sodium Carbonate → 4-[4-(5-fluoro-2-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]cyclohex-3-ene-1-carboxylic acid

HRID 528006Notes

Reaction equation

HRID 528006 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([C:8]2[C:9]3[CH:16]=[C:15](I)[NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH:7]=1.CC1(C)C(C)(C)OB([C:28]2[CH2:33][CH2:32][CH:31]([C:34]([O:36]CC)=[O:35])[CH2:30][CH:29]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>C(COC)OC.C(O)C.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([C:8]2[C:9]3[CH:16]=[C:15]([C:28]4[CH2:33][CH2:32][CH:31]([C:34]([OH:36])=[O:35])[CH2:30][CH:29]=4)[NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 592787964-(4,4,5,5-Tetramethyl-(1,3,2)dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylic acid ethyl esterHCID 90418660HCID 90418660, compound

Product 1

HCID 862714854-[4-(5-fluoro-2-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]cyclohex-3-ene-1-carboxylic acid

Reagents, catalysts & solvents 1

HCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of Example 61A (300 mg, 0.813 mmol) and ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate (342 mg, 1.219 mmol) in 10 mL dimethoxyethane/ethanol/water (7:2:3) was added sodium carbonate (345 mg, 3.25 mmol) and dichlorobis(triphenylphosphine) palladium(II) (17.09 mg, 0.024 mmol). The reaction was stirred at 90° C. for 12 hours, then cooled, and extracted with ethyl acetate. The combined organic fractions were washed with saturated sodium bicarbonate (2×), water, and brine, dried over magnesium sulfate and concentrated. The crude material was triturated with ethyl acetate, and the solid was collected by filtration. The solid was dissolved in 15 mL dioxane, treated with 6 M sodium hydroxide (1.355 ml, 8.13 mmol) and stirred at 90° C. for 12 hours. Most of the solvent was removed, and the residue was diluted with 30 mL water. The aqueous mixture was extracted with ethyl acetate (2×), and the organic fractions were discarded. The aqueous layer was made neutral (˜pH 7) with 1 M HCl. The solid was collected by filtration and dried under high-vacuum to give the title compound. 1H NMR (500 MHz, DMSO-d6) δ 12.16 (s, 1H) 8.75 (s, 1H) 7.28-7.39 (m, 2H) 7.15-7.26 (m, 1H) 6.60 (s, 1H) 6.24 (s, 1H) 3.69-3.85 (m, 3H) 2.26-2.47 (m, 4H) 1.93-2.10 (m, 1H) 1.54-1.77 (m, 1H) MS (ESI+) m/z 368.2 (M+H)+.

Workup

  1. temperaturecooled
  2. extractionextracted with ethyl acetate
  3. washThe combined organic fractions were washed with saturated sodium bicarbonate (2×), water, and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude material was triturated with ethyl acetate
  7. filtrationthe solid was collected by filtration
  8. dissolutionThe solid was dissolved in 15 mL dioxane
  9. stirringstirred at 90° C. for 12 hours
  10. customMost of the solvent was removed
  11. additionthe residue was diluted with 30 mL water
  12. extractionThe aqueous mixture was extracted with ethyl acetate (2×)
  13. filtrationThe solid was collected by filtration
  14. customdried under high-vacuum

Sources & evidence

ORD record
ord-2d01be846a4b4f13b94e9975f5759446
Source dataset
uspto-grants-2016_05
Patent number
US09346813B2

Reaction notes

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