Potassium Phosphate, Tribasic → US10023592, Example 289

HRID 518499Notes

Reaction equation

HRID 518499 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:10][CH:11]([F:13])[F:12])[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:12][CH:11]([F:13])[O:10][C:4]1[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=[C:2]([C:23]2[CH:22]=[C:21]([NH:24][S:25]([CH2:28][CH3:29])(=[O:26])=[O:27])[CH:20]=[CH:19][C:18]=2[O:17][C:16]2[CH:39]=[CH:40][C:41]([F:43])=[CH:42][C:15]=2[F:14])[CH:3]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180220745-Bromo-3-(difluoromethoxy)-1-methylpyridin-2-oneHCID 124081953N-(4-(2,4-difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanesulfonamide

Product 1

HCID 118021683US10023592, Example 289Yield 14.8%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5-bromo-3-(difluoromethoxy)-1-methylpyridin-2-one (50 mg, 0.20 mmol), N-[4-(2,4-difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethanesulfonamide (88 mg, 0.18 mmol), Pd(dppf)Cl2 (11 mg) and K3PO4 (85 mg, 0.40 mmol) in dioxane (5 mL) and water (5 drops) was purged with nitrogen, capped, and heated to 70° C. for 8 h. After the mixture was filtered, the filtrate was concentrated in vacuo and purified by prep-HPLC to afford the title compound (13 mg, 13%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 7.53 (m, 2H) 7.25 (m, 1H) 7.05 (m, 1H) 7.12 (m, 1H) 7.02-6.97 (m, 2H) 6.97-6.95 (m, 1H) 6.77 (m, 1H) 6.48 (bs, 1H) 3.67 (s, 3H) 3.15 (q, J=7.4 Hz, 2H) 1.42 (t, J=7.4 Hz, 3H). LCMS (M+H)+=487.

Workup

  1. customwas purged with nitrogen
  2. customcapped
  3. filtrationAfter the mixture was filtered
  4. concentrationthe filtrate was concentrated in vacuo
  5. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-90c4a2b0c2204a918d0b741404726603
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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