Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 4-fluoro-5-(3-fluoro-2-methyl-5-(3-(pyridin-2-yl)oxetan-3-ylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1892556Notes

Reaction equation

HRID 1892556 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:12]2[CH:13]=[CH:14][C:15]3[O:19][C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)=[C:17]([C:27](=[O:30])[NH:28][CH3:29])[C:16]=3[C:31]=2[F:32])[C:10]=1[CH3:11])[C:5](O)=[O:6].Cl.Cl.[N:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[C:41]1([NH2:45])[CH2:44][O:43][CH2:42]1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[F:32][C:31]1[C:16]2[C:17]([C:27]([NH:28][CH3:29])=[O:30])=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[O:19][C:15]=2[CH:14]=[CH:13][C:12]=1[C:9]1[CH:8]=[C:4]([C:5](=[O:6])[NH:45][C:41]2([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][N:35]=3)[CH2:42][O:43][CH2:44]2)[CH:3]=[C:2]([F:1])[C:10]=1[CH3:11]

Participants

6

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 584729003-Fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acidHCID 679580363-(pyridin-2-yl)oxetan-3-amine 2HCl

Product 1

HCID 573367934-fluoro-5-(3-fluoro-2-methyl-5-(3-(pyridin-2-yl)oxetan-3-ylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (0.050 g, 0.114 mmol, 1.0 eq) and 3-(pyridin-2-yl)oxetan-3-amine 2HCl (0.03 g, 0.134 mmol, 1.2 eq) in DMF at 0° C. was added TEA (0.15 ml, 1.08 mmol, 9 eq) and BOP reagent (0.06 g, 0.136 mmol, 1.2 eq). The reaction mixture was stirred as rt overnight. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 filtered and the filtrate concentrated. The crude product was purified by preparative HPLC. Yield: 0.010 g (15.3%).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated
  6. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-cf7269d411c240a6bbaaa74969aee0b1
Source dataset
uspto-grants-2013_08
Patent number
US08507683B2

Reaction notes

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