Potassium Hydroxide → N-(2-Fluoro-4-iodo-phenyl)-2-pyrimidin-4-ylmethyl-malonamic acid ethyl ester

HRID 450114노트

반응식

HRID 450114 반응식
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([I:15])=[CH:11][C:10]=1[F:16])=[O:7])[CH3:2].Cl[CH2:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][N:21]=1.[OH-].[K+]>>[CH2:1]([O:3][C:4](=[O:17])[CH:5]([CH2:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][N:21]=1)[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([I:15])=[CH:11][C:10]=1[F:16])=[O:7])[CH3:2]

참가 물질

4

반응물 3

HCID 14797Potassium HydroxideHCID 131235534-(Chloromethyl)pyrimidineHCID 67234460N-(2-Fluoro-4-iodo-phenyl)-malonamic acid ethyl ester

생성물 1

HCID 67234244N-(2-Fluoro-4-iodo-phenyl)-2-pyrimidin-4-ylmethyl-malonamic acid ethyl ester수율 40%

실험 절차

N-(2-Fluoro-4-iodo-phenyl)-malonamic acid ethyl ester (20.5 g, 58.4 mmol), 4-chloromethyl-pyrimidine (5.0 g, 38.9 mmol) and potassium hydroxide (3.28 g, 58.4 mmol) were dissolved in IMS (200 mL). The reaction mixture was stirred at room temperature for 16 hours then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (30 mL), washed with water (20 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 10-40% ethyl acetate in cyclohexane) to yield the title compound as an off-white solid (6.9 g, 39%). LCMS (Method B): RT=3.29 min, M+H+=444.

후처리

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in ethyl acetate (30 mL)
  3. washwashed with water (20 mL)
  4. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
  5. washThe combined organic fractions were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-c7e31450bb88434181654ae2ffe64e7d
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486963B2

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