三苯基膦 → N-{3-[3-(4-benzyloxybutyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

HRID 75679

反应方程式

HRID 75679 反应方程式
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:11]([CH3:34])[C:12](=[O:33])[C:13]([CH3:32])=[C:14]2[C:19]=1[C:18](=[O:20])[NH:17][C:16](=[O:21])[N:15]2[C:22]1[CH:23]=[C:24]([NH:28][C:29](=[O:31])[CH3:30])[CH:25]=[CH:26][CH:27]=1.[CH2:35]([O:42][CH2:43][CH2:44][CH2:45][CH2:46]O)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.C(OCC)(=O)C.O>[CH2:35]([O:42][CH2:43][CH2:44][CH2:45][CH2:46][N:17]1[C:18](=[O:20])[C:19]2=[C:10]([NH:9][C:3]3[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=3[F:1])[N:11]([CH3:34])[C:12](=[O:33])[C:13]([CH3:32])=[C:14]2[N:15]([C:22]2[CH:23]=[C:24]([NH:28][C:29](=[O:31])[CH3:30])[CH:25]=[CH:26][CH:27]=2)[C:16]1=[O:21])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

参与物

8

反应物 4

HCID 11776三苯基膦2 次HCID 75555偶氮二甲酸二异丙酯2 次HCID 5622124-苄氧基-1-丁醇2 次HCID 59717419N-{3-[5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

产物 1

HCID 59717314N-{3-[3-(4-benzyloxybutyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide收率 77%

试剂、催化剂与溶剂 3

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 8028四氢呋喃溶剂HCID 8857乙酸乙酯溶剂

实验过程

Under argon atmosphere, to a suspension of N-{3-[5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 89 (75.0 mg), 4-benzyloxybutyl alcohol 90 (25.0 μl) and triphenylphosphine (37.0 mg) in tetrahydrofuran (1.00 ml) was added diisopropyl azodicarboxylate (28.0 μl) with stirring under ice cooling. The mixture was stirred at the same temperature for 2 hrs, and 4-benzyloxybutyl alcohol (13.0 μl), triphenylphosphine (19.0 mg) and diisopropyl azodicarboxylate (14.0 μl) were added. The mixture was stirred at the same temperature for 1 hr, and water and ethyl acetate were added to allow partitioning. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (chloroform:ethyl acetate=2:1→1:1) and thin layer chromatography (hexane:acetone=1:1) for further purification to give N-{3-[3-(4-benzyloxybutyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 91 (74 mg, yield 77%) as a pale-yellow amorphous form.

后处理

  1. stirringThe mixture was stirred at the same temperature for 2 hrs
  2. stirringThe mixture was stirred at the same temperature for 1 hr
  3. customto allow partitioning
  4. washThe organic layer was washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (chloroform:ethyl acetate=2:1→1:1) and thin layer chromatography (hexane:acetone=1:1) for further purification

来源与证据

ORD记录
ord-1106c38fde70447aabef97bdc5801f08
来源数据集
uspto-grants-2014_09
专利号
US08835443B2

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