Triethylamine → 3-[5-chloro-2-methyl-4-(6-methyl-pyridin-2-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-N-methoxy-4,N-dimethyl-benzamide

HRID 2172626Notes

Reaction equation

HRID 2172626 reaction equation
CO[C:3](=[O:29])[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]([CH3:27])[N:22]=3)[N:13]=[C:12]2[CH3:28])[CH:5]=1.[OH-].[Na+].[C:32](N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:45][N:46](C)[OH:47].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:46]([O:47][CH3:32])[CH3:45])=[O:29])[C:12]([CH3:28])=[N:13][C:14]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[N:22]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 27969N,N-dimethylhydroxylamine hydrochlorideHCID 682631,1'-CarbonyldiimidazoleHCID 866862993-[5-chloro-2-methyl-4-(6-methyl-pyridin-2-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester

Product 1

HCID 715816383-[5-chloro-2-methyl-4-(6-methyl-pyridin-2-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-N-methoxy-4,N-dimethyl-benzamideYield 63.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-[5-chloro-2-methyl-4-(6-methyl-pyridin-2-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester from Step A (108 mg, 0.26 mmol) in tetrahydrofuran (1 mL) was added 1N sodium hydroxide (1 mL) and the solution stirred at ambient temperature for eighteen hours. The solution was concentrated in vacuo and the aqueous residue was 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 an orange oil which was used without any additional purification. To a solution of the crude acid in tetrahydrofuran (2 mL) was added 1,1′-carbonyldiimidazole (63 mg, 0.39 mmol). After stifling at ambient temperature for one hour, N,N-dimethylhydroxylamine HCl (38 mg, 0.39 mmol) and triethylamine (0.07 mL, 0.52 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 light brown oil (73 mg, 63%). MS (M+H): 443

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 an orange oil which
  8. customwas used without any additional purification
  9. stirringto stir for eighteen hours
  10. customThe solution was partitioned between ethyl acetate and water
  11. washThe organic layer was washed with saturated sodium bicarbonate, water, and brine
  12. dry with materialdried over magnesium sulfate
  13. filtrationThe slurry was filtered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-5ca8034012ba4a5fb5ee69db4a86ab52
Source dataset
uspto-grants-2015_06
Patent number
US09056110B2

Reaction notes

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