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

HRID 2172599
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HRID 2172599 반응식
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][C:24]([F:27])=[CH:23][CH: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][C:24]([F:27])=[CH:23][CH:22]=1
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참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 27969N,N-dimethylhydroxylamine hydrochlorideHCID 682631,1'-CarbonyldiimidazoleHCID 86686286HCID 86686286, 화합물

생성물 1

HCID 715815703-[5-chloro-4-(4-fluoro-benzyloxy)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-N-methoxy-4,N-dimethyl-benzamide
수율 90%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of 3-[5-chloro-4-(4-fluoro-benzyloxy)-2-methyl-6-oxo-6H-pyrimidin-1-yl]-4-methyl-benzoic acid methyl ester from Step A (63 mg, 0.15 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 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 (37 mg, 0.23 mmol). After stifling at ambient temperature for one hour, N,N-dimethylhydroxylamine HCl (22 mg, 0.23 mmol) and triethylamine (0.04 mL, 0.30 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 (60 mg, 90%). MS (M+H): 446

후처리

  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

출처 및 근거

ORD 기록
ord-ff48df7573264cc4bf64664c3e189e4e
출처 데이터셋
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09056110B2

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