Potassium Phosphate, Tribasic → 2,6-Difluoro-3-[4-(4-methoxy-phenyl)-5-pyridin-3-yl-thiazol-2-ylmethoxy]-benzamide

HRID 538513ノート

反応式

HRID 538513 の反応式
Br[C:2]1[S:6][C:5]([CH2:7][O:8][C:9]2[C:10]([F:19])=[C:11]([C:15]([F:18])=[CH:16][CH:17]=2)[C:12]([NH2:14])=[O:13])=[N:4][C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30](B(O)O)[CH:29]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:19][C:10]1[C:9]([O:8][CH2:7][C:5]2[S:6][C:2]([C:30]3[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=3)=[C:3]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:4]=2)=[CH:17][CH:16]=[C:15]([F:18])[C:11]=1[C:12]([NH2:14])=[O:13]

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 594026583-[5-Bromo-4-(4-methoxy-phenyl)-thiazol-2-ylmethoxy]-2,6-difluoro-benzamide

生成物 1

HCID 594028712,6-Difluoro-3-[4-(4-methoxy-phenyl)-5-pyridin-3-yl-thiazol-2-ylmethoxy]-benzamide収率 551.3%

試薬・触媒・溶媒 2

HCID 21584511triphenylphosphine palladium (II)触媒HCID 21962138N,N-Dimethylformamide--water (1/1)溶媒

反応条件

温度
120 °C

実験手順

To a solution of 3-[5-bromo-4-(4-methoxy-phenyl)-thiazol-2-ylmethoxy]-2,6-difluoro-benzamide (0.1 g, 0.02 mmol) in DMF:H2O (2:1), 3-pyridine boronic acid (0.054 g, 0.04 mmol), potassium phosphate (0.056 g, 0.025 mmol) was added. The reaction mixture was degassed for 10 min and then dichlorobis[(triphenylphosphine)-Palladium (II) (0.023 g, 0.003 mmol) was added and again degassed for 10 min. The reaction mixture was heated at 120° C. for 12 h under the nitrogen atmosphere. DMF was distilled off, after cooling to r.t., water was added into reaction mixture and extracted with ethyl acetate, The combined organic layers were dried over anhydrous Na2SO4, and evaporated to dryness under reduced pressure. The compound was purified by chromatography on silica (230-4000 using ethyl acetate/hexane (50:50) as the eluent to provide the title compound as yellow solid (0.050 g, 50%). 1H NMR (DMSO-d6, 400 MHz): δ 3.75 (s, 3H), 5.59 (s, 2H), 6.92 (d, 2H, J=8.8 Hz (o-coupling), 7.14 (dt, 1H, J=9.2 Hz (o-coupling), 7.36 (d, 2H, J=8.4 Hz (o-coupling), 7.45 (dt, 2H, J=9.2 Hz (o-coupling) J=5.2 Hz (o-coupling), 7.79 (m, 1H), 7.88 (broad s, 1H), 8.16 (broad s, 1H), 8.53 (d, 1H, J=2.0 Hz (m-coupling), 8.57 (d, 1H, J=4.8 Hz). MS ES+ (454.10), HPLC (method 5) Rt=15.26 min.

後処理

  1. customThe reaction mixture was degassed for 10 min
  2. additionwas added
  3. customagain degassed for 10 min
  4. distillationDMF was distilled off
  5. temperatureafter cooling to r.t.
  6. additionwater was added into reaction mixture
  7. extractionextracted with ethyl acetate
  8. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  9. customevaporated to dryness under reduced pressure
  10. customThe compound was purified by chromatography on silica (230-4000 using ethyl acetate/hexane (50:50) as the eluent

出典と根拠

ORDレコード
ord-e4bb33292f9149e58fdd161b6c295d12
出典データセット
uspto-grants-2014_10
特許番号
US08865736B2

反応ノート

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