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

HRID 2172634
ノート
印刷プレビュー

反応式

HRID 2172634 の反応式
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]([F: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]([F:27])[N:22]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 27969N,N-dimethylhydroxylamine hydrochlorideHCID 682631,1'-CarbonyldiimidazoleHCID 86686301HCID 86686301、化合物

生成物 1

HCID 715816413-[5-chloro-4-(6-fluoro-pyridin-2-ylmethoxy)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-N-methoxy-4,N-dimethyl-benzamide
収率 44.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of 3-[5-chloro-4-(6-fluoro-pyridin-2-ylmethoxy)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester from Step B (180 mg, 0.43 mmol) in tetrahydrofuran (2 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 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 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 (105 mg, 0.65 mmol). After stirring at ambient temperature for one hour, N,N-dimethylhydroxylamine HCl (63 mg, 0.65 mmol) and triethylamine (0.12 mL, 0.86 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 (85 mg, 44%). MS (M+H): 447

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
  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

出典と根拠

ORDレコード
ord-65d92ffa3c454fcdb46cc6b3c0c31e58
出典データセット
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09056110B2

反応ノート

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