Potassium Phosphate, Tribasic → US10023592, Example 392

HRID 518549Notes

Reaction equation

HRID 518549 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2CC(C)(C)C(C)(C)C2)[CH:5]=[C:4]([C:17]([F:20])([F:19])[F:18])[C:3]1=[O:21].Br[C:23]1[CH:37]=[C:36]([S:38]([CH2:41][CH3:42])(=[O:40])=[O:39])[CH:35]=[CH:34][C:24]=1[O:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=1[F:33].[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:33][C:27]1[CH:28]=[C:29]([F:32])[CH:30]=[CH:31][C:26]=1[O:25][C:24]1[CH:34]=[CH:35][C:36]([S:38]([CH2:41][CH3:42])(=[O:40])=[O:39])=[CH:37][C:23]=1[C:6]1[CH:5]=[C:4]([C:17]([F:18])([F:19])[F:20])[C:3](=[O:21])[N:2]([CH3:1])[CH:7]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180217871-(2-Bromo-4-ethylsulfonylphenoxy)-2,4-difluorobenzeneHCID 1317333601-Methyl-5-(3,3,4,4-tetramethylborolan-1-yl)-3-(trifluoromethyl)pyridin-2-one

Product 1

HCID 118021884US10023592, Example 392Yield 34%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

A mixture of 1-methyl-5-(3,3,4,4-tetramethylborolan-1-yl)-3-(trifluoromethyl)pyridin-2-one (100 mg, 0.33 mmol), 1-(2-bromo-4-ethylsulfonylphenoxy)-2,4-difluorobenzene (100 mg, 0.27 mmol), Pd(dppf)Cl2 (24 mg) and K3PO4 (107 mg, 0.80 mmol) in dioxane (4 mL) and water (1 mL) was purged with nitrogen, capped, and heated to 90° C. for 4 h. After the mixture was filtered through a short bed of celite, the filtrate was concentrated in vacuo and purified by prep-HPLC afford the title compound (43 mg, 34%) as a white solid. 1H NMR (CDCl3, 400 MHz) □ ppm 8.11 (s, 1H) 7.88 (s, 2H) 7.80 (m, 1H), 7.23-7.10 (m, 1H) 7.09-6.91 (m, 2H) 6.91-6.78 (m, 1H) 6.25 (s, 1H) 3.70 (s, 3H) 3.15 (q, J=7.2 Hz, 2H) 1.31 (t, J=7.2 Hz, 3H). LCMS (M+H)+=474.

Workup

  1. customwas purged with nitrogen
  2. customcapped
  3. filtrationAfter the mixture was filtered through a short bed of celite
  4. concentrationthe filtrate was concentrated in vacuo
  5. custompurified

Sources & evidence

ORD record
ord-82254af2116a470a8f9dc9b8c1a4f139
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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