4-(7-bromo-benzooxazol-2-ylamino)-2,N,N-trimethyl-benzamide → 4-[7-(3-Fluoro-4-morpholin-4-ylmethyl-phenyl)-benzooxazol-2-ylamino]-2,N,N-trimethyl-benzamide

HRID 469820Notes

Reaction equation

HRID 469820 reaction equation
Br[C:2]1[C:10]2[O:9][C:8]([NH:11][C:12]3[CH:22]=[CH:21][C:15]([C:16]([N:18]([CH3:20])[CH3:19])=[O:17])=[C:14]([CH3:23])[CH:13]=3)=[N:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[F:24][C:25]1[CH:37]=[C:36]([Sn](C)(C)C)[CH:35]=[CH:34][C:26]=1[CH2:27][N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:24][C:25]1[CH:37]=[C:36]([C:2]2[C:10]3[O:9][C:8]([NH:11][C:12]4[CH:22]=[CH:21][C:15]([C:16]([N:18]([CH3:20])[CH3:19])=[O:17])=[C:14]([CH3:23])[CH:13]=4)=[N:7][C:6]=3[CH:5]=[CH:4][CH:3]=2)[CH:35]=[CH:34][C:26]=1[CH2:27][N:28]1[CH2:29][CH2:30][O:31][CH2:32][CH2:33]1

Participants

5

Reactant 2

HCID 674578214-(7-bromo-benzooxazol-2-ylamino)-2,N,N-trimethyl-benzamideHCID 674580834-(2-Fluoro-4-trimethylstannanyl-benzyl)-morpholine

Product 1

HCID 591443124-[7-(3-Fluoro-4-morpholin-4-ylmethyl-phenyl)-benzooxazol-2-ylamino]-2,N,N-trimethyl-benzamide

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

0.1 g (0.267 mmol) 4-(7-bromo-benzooxazol-2-ylamino)-2,N,N-trimethyl-benzamide and 0.17 g (0.305 mmol) 4-(2-fluoro-4-trimethylstannanyl-benzyl)-morpholine are dissolved in 2 ml 1,2-dimethoxy-ethane and a stream of argon is bubbled through the mixture in order to exclude oxygen from the reaction mixture. Tetrakis (triphenylphosphine) palladium (0.020 g, 0.016 mmol) is added and the reaction mixture is stirred at 150° C. for 1 h. After that the reaction mixture is poured on water and extracted 3× with EtOAc. The combined organic layers are washed with water and saturated NaCl solution, dried over MgSO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography (silicagel, EtOAc:MeOH=95:5; column chromatography followed by thick-layer chromatography) to afford the title compound. Rt=1.67 min (Waters Symmetry C8, 2.1×50 mm, detection 210-250 nM, 5% to 100% CH3CN in H2O in 2 min+0.05% TFA, flow rate 1.0 ml/min); MS: 375 (M+1)+.

Workup

  1. customa stream of argon is bubbled through the mixture in order
  2. additionAfter that the reaction mixture is poured on water
  3. extractionextracted 3× with EtOAc
  4. washThe combined organic layers are washed with water and saturated NaCl solution
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate is concentrated in vacuo
  8. customThe residue is purified by chromatography (silicagel, EtOAc:MeOH=95:5; column chromatography followed by thick-layer chromatography)

Sources & evidence

ORD record
ord-894fdc4cb1594457a4992f6135d91a5b
Source dataset
uspto-grants-2014_01
Patent number
US08629168B2

Reaction notes

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