Water → 2,6-Difluoro-3-[5-(3-methoxy-phenyl)-benzothiazol-2-ylmethoxy]-benzamide

HRID 538521노트

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HRID 538521 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH2:10][O:11][C:12]3[C:13]([F:22])=[C:14]([C:18]([F:21])=[CH:19][CH:20]=3)[C:15]([NH2:17])=[O:16])=[N:7][C:6]=2[CH:23]=1.O.[CH3:25][O:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:22][C:13]1[C:12]([O:11][CH2:10][C:8]2[S:9][C:5]3[CH:4]=[CH:3][C:2]([C:31]4[CH:30]=[CH:29][CH:28]=[C:27]([O:26][CH3:25])[CH:32]=4)=[CH:23][C:6]=3[N:7]=2)=[CH:20][CH:19]=[C:18]([F:21])[C:14]=1[C:15]([NH2:17])=[O:16]

참가 물질

7

반응물 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2734370(3-Methoxyphenyl)boronic acidHCID 462370143-(5-Bromo-benzothiazol-2-ylmethoxy)-2,6-difluoro-benzamide

생성물 1

HCID 594028792,6-Difluoro-3-[5-(3-methoxy-phenyl)-benzothiazol-2-ylmethoxy]-benzamide수율 43.5%

시약·촉매·용매 2

HCID 21584511triphenylphosphine palladium (II)촉매HCID 6228Dimethylformamide용매

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온도
120 °C

실험 절차

To the solution of compound 3-(5-bromo-benzothiazol-2-ylmethoxy)-2,6-difluoro-benzamide (0.300 g, 0.755 mmol) in dry DMF:H2O (5 mL: 2.5 mL), added 3-methoxyphenyl boronic acid (0.228 g, 1.5 mmol), and K3PO4 (0.190 g, 0.9 mmol) under the inert condition at room temperature and degassed for half an hour. Then to the reaction mixture added dichlorobis[(triphenylphosphine)-palladium (II) (0.078 g, 0.075 mmol) and again degassed for half an hour. The reaction mixture was heated at 120° C. for 2 hrs under 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 (230-400μ) using ethyl acetate/hexane (50:50 as the eluent to provide the title compound as white solid (0.140 g, 43%). 1H NMR (DMSO-d6, 400 MHz); δ 3.85 (s, 3H), 5.72 (s, 2H), 6.97 (t, 1H, J=6.8 Hz (o-coupling), 7.11 (t, 1H, J=8.8 Hz, (o-coupling), 7.30 (broad s, 1H), 7.34 (d, 1H, J=8.8 Hz (o-coupling), 7.40 (dd, 2H, J=8.0 Hz (o-coupling), 7.79 (d, 1H, J=8.0 Hz (o-coupling), 7.90 (broad s, 1H), 8.18 (broad s, 1H), 8.21 (d, 1H, J=8.0 Hz); MS ES+ (427.14), HPLC (method 5) Rt=16.48 min.

후처리

  1. customdegassed for half an hour
  2. customagain degassed for half an hour
  3. distillationDMF was distilled off
  4. temperatureafter cooling to r.t. water
  5. additionwas added into reaction mixture
  6. extractionextracted with ethyl acetate
  7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  8. customevaporated to dryness under reduced pressure
  9. customThe compound was purified by chromatography on silica (230-400μ)

출처 및 근거

ORD 기록
ord-26d4c553b8ed4432a9703ea14c83579d
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865736B2

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