Potassium Phosphate, Tribasic → US10023592, Example 269

HRID 575758Notes

Reaction equation

HRID 575758 reaction equation
Br[C:2]1[C:3]2[CH:12]=[C:11]([CH3:13])[O:10][C:4]=2[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[F:14][C:15]1[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:16]=1[O:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][S:25]([CH2:28][CH3:29])(=[O:27])=[O:26])=[CH:20][C:19]=1B1OC(C)(C)C(C)(C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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]>[F:14][C:15]1[CH:42]=[C:41]([F:43])[CH:40]=[CH:39][C:16]=1[O:17][C:18]1[CH:19]=[CH:20][C:21]([NH:24][S:25]([CH2:28][CH3:29])(=[O:26])=[O:27])=[CH:22][C:23]=1[C:2]1[C:3]2[CH:12]=[C:11]([CH3:13])[O:10][C:4]=2[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180215124-Bromo-2,6-dimethylfuro[2,3-c]pyridin-7-oneHCID 124081953N-(4-(2,4-difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanesulfonamide

Product 1

HCID 118021620US10023592, Example 269Yield 12%

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
70 °C

Procedure

A mixture of 4-bromo-2,6-dimethylfuro[2,3-c]pyridin-7-one (200 mg, 0.83 mol), N-[4-(2,4-difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethanesulfonamide (364 mg, 0.99 mmol), Pd(dppf)Cl2 (66 mg, 0.09 mmol), K3PO4 (527 mg, 2.49 mmol) in dioxane/water (4 mL/1 mL) was bubbled with argon for 5 min. The mixture was heated to 70° C. for 18 h. After cooling to rt, the reaction mixture was poured into water (10 mL) and extracted with EtOAc (40 mL×3). The combined organic layers were washed with brine (20 mL×2), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by prep-HPLC to afford the title compound (49 mg, 12%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 7.35-7.33 (m, 2H) 7.12 (m, 1H) 6.95-6.89 (m, 2H) 6.81 (m, 2H) 6.43 (s, 1H) 6.38 (s, 1H) 3.71 (s, 3H) 3.16 (q, J=7.2 Hz, 2H) 2.47 (s, 3H) 1.43 (t, J=7.2 Hz, 3H). LCMS (M+H)+=475.

Workup

  1. customwas bubbled with argon for 5 min
  2. temperatureAfter cooling to rt
  3. additionthe reaction mixture was poured into water (10 mL)
  4. extractionextracted with EtOAc (40 mL×3)
  5. washThe combined organic layers were washed with brine (20 mL×2)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-cb90f542eb5a4c2e903a108d312eaab0
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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