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Methanol → 2-(2,6-Difluorophenyl)-5-(pyridin-2-yl)oxazole-4-carboxamide

HRID 389712
Notes
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Reaction equation

HRID 389712 reaction equation
Br[C:2]1[O:6][C:5]([C:7]2[C:12]([F:13])=[CH:11][CH:10]=[CH:9][C:8]=2[F:14])=[N:4][C:3]=1[C:15]#[N:16].C([Sn](CCCC)(CCCC)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)CCC.C[OH:37]>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:14][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]([F:13])[C:7]=1[C:5]1[O:6][C:2]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[C:3]([C:15]([NH2:16])=[O:37])[N:4]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 887MethanolHCID 6077842-(Tributylstannyl)pyridineHCID 595875125-Bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrile

Product 1

HCID 251203512-(2,6-Difluorophenyl)-5-(pyridin-2-yl)oxazole-4-carboxamideYield 58%

Reagents, catalysts & solvents 2

HCID 178418397
HCID 178418397, compound
Catalyst
HCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 5-bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrile (0.050 g, 0.16 mmol), tri-n-butyl(2-pyridyl)tin (0.120 g, 0.32 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.010 g, 0.008 mmol) in acetonitrile (2.5 mL) was heated in the microwave for 15 minutes at 150° C. The reaction was diluted with MeOH and passed through a MP-SH resin cartridge (0.5 g), then purified by SPE using a MP-TsOH resin (500 mg) cartridge and the solvent removed in vacuo. The residue was purified by preparative HPLC to afford 2-(2,6-difluorophenyl)-5-(pyridin-2-yl)oxazole-4-carboxamide (0.029 g, 0.10 mmol, 58%) as a white solid. 1H NMR (DMSO) 7.41 (2H, t), 7.55 (1H, ddd), 7.76 (1H, m), 7.88 (1H, br. s), 8.06 (1H, ddd), 8.32 (1H, dt), 8.77 (1H, ddd), 9.10 (1H, br. s). LCMS (2) Rt: 2.23 min; m/z (ES+) 302.

Workup

  1. custompurified by SPE
  2. customthe solvent removed in vacuo
  3. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-cda855d08b4f4bcd916aa51ba311e87d
Source dataset
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08378095B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes