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

HRID 415595Notes

Reaction equation

HRID 415595 reaction equation
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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 21584511triphenylphosphine palladium (II)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

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, 1 H, 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.

Workup

  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)

Sources & evidence

ORD record
ord-d523600769d248298dff6b5e17fa2ffa
Source dataset
uspto-grants-2012_01
Patent number
US08088791B2

Reaction notes

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