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Potassium Phosphate, Tribasic → US10023592, Example 292

HRID 575772
Notes
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Reaction equation

HRID 575772 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[F:16][C:17]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:18]=1[O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][S:27]([CH2:30][CH3:31])(=[O:29])=[O:28])=[CH:22][C:21]=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:16][C:17]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:18]=1[O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][S:27]([CH2:30][CH3:31])(=[O:29])=[O:28])=[CH:22][C:21]=1[C:2]1[CH:3]=[C:4]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180227245-Bromo-1-methyl-3-(2,2,2-trifluoroethoxy)pyridin-2-oneHCID 1239573972-[2-(2,4-Difluorophenoxy)-5-(ethylsulfonylmethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 118022018US10023592, Example 292Yield 22.5%

Reagents, catalysts & solvents 3

HCID 962
Water
Catalyst
HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst
HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5-bromo-1-methyl-3-(2,2,2-trifluoroethoxy)pyridin-2-one (50 mg, 0.18 mmol), 2-[2-(2,4-difluorophenoxy)-5-(ethylsulfonylmethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (88 mg, 0.20 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 (21 mg, 22%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 7.41 (m, 2H) 7.35 (m, 1H) 7.30 (m, 1H) 7.07-6.96 (m, 2H) 6.92-6.87 (m, 1H) 6.80 (m, 1H), 4.51 (m, 2H) 4.21 (s, 2H) 3.69 (s, 3H) 2.97 (m, 2H) 1.44 (m, 3H). LCMS (M+H)+=518.

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-f72129b670854c9196741c065eec6036
Source dataset
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09034900B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes