4-Aminobenzoic Acid → 4-(4-Cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)benzoic acid

HRID 389777ノート

反応式

HRID 389777 の反応式
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Br[C:44]1[O:48][C:47]([C:49]2[C:54]([F:55])=[CH:53][CH:52]=[CH:51][C:50]=2[F:56])=[N:46][C:45]=1[C:57]#[N:58].[NH2:59][C:60]1[CH:68]=[CH:67][C:63]([C:64]([OH:66])=[O:65])=[CH:62][CH:61]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(O)CCC.O1CCOCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:57]([C:45]1[N:46]=[C:47]([C:49]2[C:54]([F:55])=[CH:53][CH:52]=[CH:51][C:50]=2[F:56])[O:48][C:44]=1[NH:59][C:60]1[CH:68]=[CH:67][C:63]([C:64]([OH:66])=[O:65])=[CH:62][CH:61]=1)#[N:58]

参加物

8

反応物 4

HCID 9784-Aminobenzoic AcidHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 595875125-Bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrile

生成物 1

HCID 595874924-(4-Cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)benzoic acid収率 14%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒HCID 67780350nBuOH dioxane溶媒

反応条件

温度
140 °C

実験手順

A solution of tris(dibenzylideneacetone)dipalladium(0) (0.337 g, 0.368 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.213 g, 0.368 mmol) in n-butanol:dioxane (1:1) (5 mL) was stirred at room temperature for 3 minutes. Then 5-bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrile (1.50 g, 5.262 mmol), 4-aminobenzoic acid (2.165 g, 15.787 mmol) and cesium carbonate (3.429 g, 10.525 mmol) were added and the mixture heated in the microwave for 3 minutes at 140° C. The reaction was diluted with EtOAc and washed with water. The organic phase was passed through an MP-SH cartridge, dried over MgSO4 and the solvent removed in vacuo. The residue was purified by column chromatography using a 20-45% EtOAc:hexane gradient then further purified by trituration of the solid in DCM:hexane (1:1) to afford 4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)benzoic acid (0.251 g, 0.735 mmol, 14%) as a light yellow solid. 1H NMR (DMSO) δ 7.34 (2H, t), 7.40 (2H, d), 7.66 (1H, m), 7.92 (2H, d), 11.16 (1H, br s), 12.76 (1H, br s). LCMS (3) Rt: 1.53 min; m/z (ES+) 342.

後処理

  1. washwashed with water
  2. dry with materialdried over MgSO4
  3. customthe solvent removed in vacuo
  4. customThe residue was purified by column chromatography
  5. customhexane gradient then further purified by trituration of the solid in DCM:hexane (1:1)

出典と根拠

ORDレコード
ord-5726640d4d5d4811a7ba24eaa86d9f53
出典データセット
uspto-grants-2013_02
特許番号
US08378095B2

反応ノート

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