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

HRID 1892562Notes

Reaction equation

HRID 1892562 reaction equation
[F:1][C:2]1[C:7]2[C:8]([C:18](=[O:21])[NH:19][CH3:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[C:23]([CH3:33])=[CH:24][C:25]([O:31][CH3:32])=[C:26]([CH:30]=1)[C:27](O)=[O:28].Cl.[N:35]1[CH:40]=[CH:39][CH:38]=[N:37][C:36]=1[C:41]1([NH2:45])[CH2:44][O:43][CH2:42]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>O>[F:1][C:2]1[C:7]2[C:8]([C:18]([NH:19][CH3:20])=[O:21])=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[CH:30]=[C:26]([C:27](=[O:28])[NH:45][C:41]2([C:36]3[N:37]=[CH:38][CH:39]=[CH:40][N:35]=3)[CH2:44][O:43][CH2:42]2)[C:25]([O:31][CH3:32])=[CH:24][C:23]=1[CH3:33]

Participants

5

Reactant 3

HCID 2724699PyBOPHCID 592754645-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl) 2-methoxy-4-methylbenzoic acidHCID 679578123-(Pyrimidin-2-yl)oxetan-3-amine hydrochloride

Product 1

HCID 679579894-fluoro-2-(4-fluorophenyl)-5-(4-methoxy-2-methyl-5-(3-(pyrimidin-2-yl)oxetan-3-ylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a yellow solution mixture of 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acid (30 mg, 0.066 mmol) and 3-(pyrimidin-2-yl)oxetan-3-amine hydrochloride (12.5 mg, 0.067 mmol) 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 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 solution was dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative HPLC. Yield (6 mg, 15%).

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 solution was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by preparative HPLC
  11. customYield (6 mg, 15%)

Sources & evidence

ORD record
ord-93a750b20d4f42818bbfa968a01024c5
Source dataset
uspto-grants-2013_08
Patent number
US08507683B2

Reaction notes

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