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

HRID 538520ノート

反応式

HRID 538520 の反応式
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.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:7][C:6]1[CH:23]=[CH:2][CH:3]=[CH:4][C:5]=1[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

参加物

6

反応物 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 462370143-(5-Bromo-benzothiazol-2-ylmethoxy)-2,6-difluoro-benzamide

生成物 1

HCID 594026683-[5-(2-Amino-phenyl)-benzothiazol-2-ylmethoxy]-2,6-difluoro-benzamide収率 16.1%

試薬・触媒・溶媒 2

HCID 21584511triphenylphosphine palladium (II)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

To the solution of compound 3-(5-bromo-benzothiazol-2-ylmethoxy)-2,6-difluoro-benzamide (0.3 g 0.755 mmol) in dry DMF:H2O (5 mL: 2.5 mL), phenylamine-2-boronic acid (0.260 g, 1.5 mmol), and K2CO3 (0.125 g, 0.9 mmol) was added under nitrogen atmosphere at room temperature. After that reaction mixture was degassed for half an hour. Dichlorobis[(triphenylphosphine)-palladium (II) was added to the reaction mixture (0.080 g, 0.113 mmol) and again degassed for half an hour and 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 yellow solid (0.025 g, 8%). 1H NMR (DMSO-d6, 400 MHz); δ 4.86 (broad s, 2H), 5.71 (s, 2H), 6.66 (dt, 1H, J=8.4 Hz (o-coupling), 6.78 (d, 1H, J=7.2 Hz (o-coupling), 7.04-7.13 (m, 3H), 7.37-7.44 (m, 1H), 7.51 (dd, 1H, J=8.4 Hz (o-coupling), J=1.6 Hz (m-coupling), 7.89 (broad s, 1H), 8.00 (broad s, 1H), 8.18 (d, 2H, J=4.0 Hz); MS ES+ (412.16), HPLC (method 5) Rt=15.33 min.

後処理

  1. customAfter that reaction mixture was degassed 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)

出典と根拠

ORDレコード
ord-08d5f84ca672447ca8d817a7326e644c
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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