Sodium Bicarbonate → US10023592, Example 368

HRID 518534Notes

Reaction equation

HRID 518534 reaction equation
Br[C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[C:5](=[O:11])[N:4]([CH3:12])[CH:3]=1.[CH:13]1([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH2:27][CH3:28])(=[O:26])=[O:25])=[CH:20][C:19]=2B2OC(C)(C)C(C)(C)O2)[CH2:15][CH2:14]1.C([O-])(O)=O.[Na+]>O1CCOCC1.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]>[CH:13]1([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH2:27][CH3:28])(=[O:26])=[O:25])=[CH:20][C:19]=2[C:2]2[N:7]3[CH:8]=[N:9][CH:10]=[C:6]3[C:5](=[O:11])[N:4]([CH3:12])[CH:3]=2)[CH2:14][CH2:15]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 896575182-[2-(Cyclopropylmethoxy)-5-(ethylsulfonyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 1180225995-Bromo-7-methylimidazo[1,5-a]pyrazin-8(7h)-one

Product 1

HCID 118021754US10023592, Example 368Yield 22%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a microwave vial containing 5-bromo-7-methylimidazo[1,5-a]pyrazin-8-one (150 mg, 0.66 mmol), 2-[2-(cyclopropylmethoxy)-5-ethylsulfonylphenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (290 mg, 0.80 mmol) and NaHCO3 (1 mL, 2M) in dioxane (3 mL) was added Pd(dppf)Cl2 (80 mg, 0.10 mmol). The mixture was purge with N2 for 2 min and sealed. The reaction was irradiated in microwave at 100° C. for 2 h. Water (20 mL) was added and the mixture was extracted with EtOAc (20 mL×3). The combined organic layers were washed with brine (20 mL), dried with Na2SO4, filtered and concentrated in vacuum. The residue was purified by column chromatography (PE: EA=5:1 to 1:1) to afford the title compound (55.3 mg, 22%) as a light yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.03 (dd, J1=8.4 Hz, J2=2.0 Hz, 2H), 7.94 (d, J=2.0 Hz, 1H), 7.56 (s, 1H), 7.15 (d, J=8.8 Hz, 1H), 6.49 (s, 1H), 3.96 (d, J=6.4 Hz, 2H), 3.54 (s, 3H), 3.16 (q, J=7.6 Hz, 1H), 1.33 (t, J=7.6 Hz, 1H), 1.08 (s, 1H), 0.54 (d, J=7.2 Hz, 2H), 0.54 (d, J=4.4 Hz, 2H). LCMS: 388.1 (M+1)+

Workup

  1. customThe mixture was purge with N2 for 2 min
  2. customsealed
  3. customThe reaction was irradiated in microwave at 100° C. for 2 h
  4. additionWater (20 mL) was added
  5. extractionthe mixture was extracted with EtOAc (20 mL×3)
  6. washThe combined organic layers were washed with brine (20 mL)
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuum
  10. customThe residue was purified by column chromatography (PE: EA=5:1 to 1:1)

Sources & evidence

ORD record
ord-8055e8780d97499792e08ec713afa3c5
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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