Triethylamine → HCID 71581639, compound

HRID 2172630Notes

Reaction equation

HRID 2172630 reaction equation
CO[C:3](=[O:32])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[C:16](=[O:17])[C:15]([Cl:18])=[C:14]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[N:22]=3)[N:13]=[C:12]2[CH3:31])[CH:5]=1.[OH-].[Na+].[C:35](N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:48][N:49](C)[OH:50].C(N(CC)CC)C>O1CCCC1>[Cl:18][C:15]1[C:16](=[O:17])[N:11]([C:6]2[CH:5]=[C:4]([CH:9]=[CH:8][C:7]=2[CH3:10])[C:3]([N:49]([O:50][CH3:35])[CH3:48])=[O:32])[C:12]([CH3:31])=[N:13][C:14]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:28])[F:29])[N:22]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 27969N,N-dimethylhydroxylamine hydrochlorideHCID 682631,1'-CarbonyldiimidazoleHCID 86686300HCID 86686300, compound

Product 1

HCID 71581639HCID 71581639, compoundYield 46.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-[5-chloro-2-methyl-6-oxo-4-(6-trifluoromethyl-pyridin-2-ylmethoxy)-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester from Step A (110 mg, 0.23 mmol) in tetrahydrofuran (1 mL) was added 1N sodium hydroxide (1 mL) and the solution was stirred at ambient temperature for eighteen hours. The solution was concentrated in vacuo and the aqueous residue acidified to pH=2 using 1M HCl. The solution was extracted with ethyl acetate, washed with water and dried over magnesium sulfate. The slurry was filtered and concentrated to give a yellow solid which was used without additional purification. To a solution of the crude acid in tetrahydrofuran (2 mL) was added 1,1′-carbonyldiimidazole (56 mg, 0.35 mmol). After stirring at ambient temperature for one hour, N,N-dimethylhydroxylamine HCl (35 mg, 0.35 mmol) and triethylamine (0.06 mL, 0.46 mmol) were added. The solution continued to stir for eighteen hours. The solution was partitioned between ethyl acetate and water. The organic layer was washed with saturated sodium bicarbonate, water, and brine and dried over magnesium sulfate. The slurry was filtered and concentrated to provide the amide as a colorless oil (53 mg, 46%). MS (M+H): 497

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. extractionThe solution was extracted with ethyl acetate
  3. washwashed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe slurry was filtered
  6. concentrationconcentrated
  7. customto give a yellow solid which
  8. customwas used without additional purification
  9. stirringAfter stirring at ambient temperature for one hour
  10. stirringto stir for eighteen hours
  11. customThe solution was partitioned between ethyl acetate and water
  12. washThe organic layer was washed with saturated sodium bicarbonate, water, and brine
  13. dry with materialdried over magnesium sulfate
  14. filtrationThe slurry was filtered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-3fa236258ffa4c499e563c3aa48450bf
Source dataset
uspto-grants-2015_06
Patent number
US09056110B2

Reaction notes

Loading…