Water → 4-fluoro-5-(3-fluoro-2-methyl-5-(3-(pyrimidin-2-yl)oxetan-3-ylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1892563Notes

Reaction equation

HRID 1892563 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.[N:34]1[CH:39]=[CH:38][CH:37]=[N:36][C:35]=1[C:40]1([NH2:44])[CH2:43][O:42][CH2:41]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.O>CN(C=O)C>[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:44][C:40]2([C:35]3[N:34]=[CH:39][CH:38]=[CH:37][N:36]=3)[CH2:43][O:42][CH2:41]2)[CH:3]=[C:2]([F:1])[C:10]=1[CH3:11]

Participants

6

Reactant 4

HCID 962WaterHCID 2724699PyBOPHCID 584729003-Fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acidHCID 679578123-(Pyrimidin-2-yl)oxetan-3-amine hydrochloride

Product 1

HCID 679577154-fluoro-5-(3-fluoro-2-methyl-5-(3-(pyrimidin-2-yl)oxetan-3-ylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a yellow solution mixture of 3-fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (30 mg, 0.068 mmol) and 3-(pyrimidin-2-yl)oxetan-3-amine hydrochloride (12.5 mg, 0.067 mmol) in DMF (1 ml) in a 25 mL round-bottomed flask was added PyBOP (50 mg, 0.096 mmol), followed by TEA (0.1 ml, 0.717 mmol), and the reaction mixture was stirred for overnight. Ice cooled water was added to the reaction mixture, which was then stirred for 10-15 min. at 0° C. Precipitation was observed. The solid was collected by filtration, washed with cold water, and then dissolved in dichloromethane. The organic was dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative HPLC. Yield (10 mg, 25%).

Workup

  1. additionwas added to the reaction mixture, which
  2. stirringwas then stirred for 10-15 min. at 0° C
  3. customPrecipitation
  4. filtrationThe solid was collected by filtration
  5. washwashed with cold water
  6. dissolutiondissolved in dichloromethane
  7. dry with materialThe organic was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by preparative HPLC
  11. customYield (10 mg, 25%)

Sources & evidence

ORD record
ord-6e1d7347c85e4bb485a5d90cf2f6bcc0
Source dataset
uspto-grants-2013_08
Patent number
US08507683B2

Reaction notes

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