Triethylamine → HCID 71581571, compound

HRID 2172613Notes

Reaction equation

HRID 2172613 reaction equation
CO[C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[C:16](=[O:17])[C:15]([Br:18])=[C:14]([O:19][CH2:20][C:21]3[N:22]=[C:23]([CH3:26])[S:24][CH:25]=3)[N:13]=[C:12]2[CH3:27])[CH:5]=1.[OH-].[Na+].[C:31](N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:44][N:45](C)[OH:46].C(N(CC)CC)C>O1CCCC1>[Br: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:45]([O:46][CH3:31])[CH3:44])=[O:28])[C:12]([CH3:27])=[N:13][C:14]=1[O:19][CH2:20][C:21]1[N:22]=[C:23]([CH3:26])[S:24][CH:25]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 27969N,N-dimethylhydroxylamine hydrochlorideHCID 682631,1'-CarbonyldiimidazoleHCID 86686295HCID 86686295, compound

Product 1

HCID 71581571HCID 71581571, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-[5-bromo-2-methyl-4-(2-methyl-thiazol-4-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester from Step B (338 mg, 0.73 mmol) in tetrahydrofuran (2 mL) was added 1N sodium hydroxide (1 mL) and the solution stirred at ambient temperature for two 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 a brown oil and used without any additional purification. To a solution of the crude acid in tetrahydrofuran (3 mL) was added 1,1′-carbonyldiimidazole (177 mg, 1.1 mmol). After stifling at ambient temperature for one hour, N,N-dimethylhydroxylamine HCl (107 mg, 1.1 mmol) and triethylamine (0.2 mL, 1.46 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 yellow oil (71 mg, 20%). MS (M, M+2): 493, 495

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 to a brown oil
  7. customused without any additional purification
  8. waitAfter stifling at ambient temperature for one hour
  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-b3b5b9fee01a4169ada0f86f9bbffab4
Source dataset
uspto-grants-2015_06
Patent number
US09056110B2

Reaction notes

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