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

HRID 2172617ノート

反応式

HRID 2172617 の反応式
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]([Cl: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>[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: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

参加物

7

反応物 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 27969N,N-dimethylhydroxylamine hydrochlorideHCID 682631,1'-CarbonyldiimidazoleHCID 866862963-[5-chloro-2-methyl-4-(2-methyl-thiazol-4-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester

生成物 1

HCID 715815723-[5-chloro-2-methyl-4-(2-methyl-thiazol-4-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-N-methoxy-4,N-dimethyl-benzamide収率 71%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of 3-[5-chloro-2-methyl-4-(2-methyl-thiazol-4-ylmethoxy)-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester from Step A (125 mg, 0.30 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 an orange oil used without any additional purification. To a solution of the crude acid in tetrahydrofuran (2 mL) was added 1,1′-carbonyldiimidazole (72 mg, 0.45 mmol). After stifling at ambient temperature for one hour, N,N-dimethylhydroxylamine HCl (44 mg, 0.45 mmol) and triethylamine (0.08 mL, 0.60 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 (93 mg, 71%). MS (M+H): 449

後処理

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

出典と根拠

ORDレコード
ord-913d201a59754f288fbaf6d007355405
出典データセット
uspto-grants-2015_06
特許番号
US09056110B2

反応ノート

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