Dimethyl Sulfoxide → methyl N-[3-(6,7-dimethoxy-2-methylaminoquinazolin-4-yl)phenyl]terephthalamic acid

HRID 41495

反応式

HRID 41495 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([O:18][CH3:19])[CH:16]=3)[N:11]=[C:10](CN)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[N:24]1C=CC=C[CH:25]=1.C[O:31][C:32](=[O:42])[C:33]1[CH:38]=[CH:37][C:36]([C:39](Cl)=[O:40])=[CH:35][CH:34]=1.[CH3:43]S(C)=O>O1CCCC1>[CH3:43][C:34]1[CH:35]=[C:36]([C:39]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]3[C:17]4[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([O:18][CH3:19])[CH:16]=4)[N:11]=[C:10]([NH:24][CH3:25])[N:9]=3)[CH:3]=2)=[O:40])[CH:37]=[CH:38][C:33]=1[C:32]([OH:31])=[O:42]

参加物

6

反応物 4

HCID 679Dimethyl SulfoxideHCID 1049PyridineHCID 81850Methyl 4-(chlorocarbonyl)benzoateHCID 25196907[4-(3-Aminophenyl)-6,7-dimethoxyquinazolin-2-yl]methylamine

生成物 1

HCID 66646296methyl N-[3-(6,7-dimethoxy-2-methylaminoquinazolin-4-yl)phenyl]terephthalamic acid収率 53.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 16.8 g of [4-(3-aminophenyl)-6,7-dimethoxyquinazolin-2-yl]methylamine and 8.6 g of pyridine dissolved in 300 mL of tetrahydrofuran was added 11.8 g of 4-chlorocarbonylbenzoic acid methyl ester at room temperature, followed by stirring for 24 hours. To the reaction mixture was added 100 mL of dimethyl sulfoxide, the mixture was partitioned between a mixed solvent consisting of 2,000 mL of ethyl acetate and 1,000 mL of tetrahydrofuran, and 1,000 mL of a saturated sodium hydrogencarbonate solution, and the organic layer was separated. The water layer was further extracted with a mixed solvent consisting of 500 mL of ethyl acetate and 500 mL of tetrahydrofuran. The combined organic layer was then washed with 1,000 mL of a saturated sodium hydrogencarbonate solution and 1,000 mL of brine in this order, and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration with 100 g of a basic silica gel pad, followed by well washing with 2,000 mL of ethyl acetate. The combined eluent was concentrated under reduced pressure, and the obtained crude product was suspended and triturated in a mixed solvent consisting of 100 mL of tetrahydrofuran and 500 mL of diethyl ether. The precipitated crystals were collected by filtration, washed twice with 100 mL of diethyl ether, and dried under aeration at 50° C. for 5 hours to yield 13.8 g of the crystals of the titled compound (yield: 53.2%).

後処理

  1. customthe mixture was partitioned between a mixed solvent
  2. customthe organic layer was separated
  3. extractionThe water layer was further extracted with a mixed solvent
  4. washThe combined organic layer was then washed with 1,000 mL of a saturated sodium hydrogencarbonate solution and 1,000 mL of brine in this order
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe desiccant was removed by filtration with 100 g of a basic silica gel pad
  7. washby well washing with 2,000 mL of ethyl acetate
  8. concentrationThe combined eluent was concentrated under reduced pressure
  9. customthe obtained crude product
  10. customtriturated in a mixed solvent
  11. filtrationThe precipitated crystals were collected by filtration
  12. washwashed twice with 100 mL of diethyl ether
  13. customdried under aeration at 50° C. for 5 hours

出典と根拠

ORDレコード
ord-b65b6dfeee5e48dbabea7bb947daa588
出典データセット
uspto-grants-2013_09
特許番号
US08530654B2

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