Sodium Bicarbonate → US10023592, Example 252

HRID 518459Notes

Reaction equation

HRID 518459 reaction equation
Br[C:2]1[C:3]2[CH:12]=[CH:11][O:10][C:4]=2[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=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.O.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[C:3]3[CH:12]=[CH:11][O:10][C:4]=3[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=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 1180214004-Bromo-6-methylfuro[2,3-c]pyridin-7-one

Product 1

HCID 118021538US10023592, Example 252Yield 25%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

A mixture of the title compound of step 2 (150 mg, 0.66 mmol), 2-[2-(cyclopropylmethoxy)-5-ethylsulfonylphenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (336 mg, 1.0 mmol), NaHCO3 (167 mg, 1.99 mmol), Pd(dppf)Cl2 (35 mg, 0.048 mmol) in dioxane/H2O (10 mL/2.5 mL) was bubbled with argon for 5 min. The sealed vial was stirred at 80° C. for 18 h. The reaction mixture was concentrated, treated with DCM (30 mL), washed with water (30 mL) and brine (30 mL), dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue was purified by prep-HPLC to give the title compound (63 mg, 25%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 7.90-7.86 (m, 2H), 7.75 (d, J=1.6 Hz, 1H), 7.31 (s, 1H), 7.09 (d, J=8.4 Hz, 1H), 6.57 (d, J=1.6 Hz, 1H), 3.95 (d, J=6.8 Hz, 2H), 3.74 (s, 3H), 3.18-3.12 (q, J=7.6 Hz, 2H), 1.34 (t, J=7.6 Hz, 3H), 1.16-1.15 (m, 1H), 0.61-0.55 (m, 2H), 0.31-0.27 (m, 2H). LCMS (M+H)+=388.

Workup

  1. customwas bubbled with argon for 5 min
  2. concentrationThe reaction mixture was concentrated
  3. additiontreated with DCM (30 mL)
  4. washwashed with water (30 mL) and brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-18aab0c172994cd5a0197408c39551c8
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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