Diethylamine → (S)-(+)-2-[6-(3-diethylamino-2-methylpropoxy)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropy-acetamide

HRID 1157463ノート

反応式

HRID 1157463 の反応式
[CH:1]([NH:4][C:5]([CH2:7][N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:19][CH2:20][C@@H:21]([CH3:28])[CH2:22]OS(C)(=O)=O)[CH:15]=2)[N:10]=[C:9]1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=1)=[O:6])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:43]([NH:45][CH2:46][CH3:47])[CH3:44].CCCCCC>C(#N)C>[CH2:43]([N:45]([CH2:46][CH3:47])[CH2:22][C@H:21]([CH3:28])[CH2:20][O:19][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=1)[N:8]([CH2:7][C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[O:6])[C:17]2=[O:18])[CH3:44]

参加物

6

反応物 4

HCID 8021DiethylamineHCID 8058HexaneHCID 11430Potassium CarbonateHCID 59511753(R)-(-)-methanesulfonic acid 3-[3-(isopropylcarbamoylmethyl)-2-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-6-yloxy]-2-methylpropyl ester

生成物 1

HCID 59511766(S)-(+)-2-[6-(3-diethylamino-2-methylpropoxy)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropy-acetamide収率 65%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
80 °C

実験手順

To a solution of (R)-(−)-methanesulfonic acid 3-[3-(isopropylcarbamoylmethyl)-2-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-6-yloxy]-2-methylpropyl ester (1.13 g, 2.18 mmol) in anhydrous acetonitrile (40 mL) was added potassium carbonate (1.51 g, 10.95 mmol) followed by diethyl amine (3.20 g, 4.53 mL, 43.80 mmol) and the reaction mixture was heated at 80° C. in a pressure tube. After 2 days (reaction complete by HPLC), the reaction mixture was concentrated in vacuo to dryness and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL). The aqueous layer was extracted with ethyl acetate (5×150 mL) and with dichloromethane (5×100 mL). The combined organic phase was dried (Na2SO4), solvent evaporated in vacuo, and the resulting residue purified by chromatography on silica gel with a gradient of methanol:dichloromethane (1:19, v/v) to methanol:dichloromethane (1:4, v/v) as eluent. The resultant solid was recrystallised from diethyl ether:hexane to afford (S)-(+)-2-[6-(3-diethylamino-2-methylpropoxy)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropy-acetamide (EXAMPLE 4a) (0.69 g, 1.40 mmol, 65% from (S)-(+)-2-[6-(3-hydroxy-2-methylpropoxy)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide) as a white solid.

後処理

  1. customAfter 2 days (reaction complete by HPLC)
  2. concentrationthe reaction mixture was concentrated in vacuo to dryness
  3. customthe residue was partitioned between water (100 mL) and ethyl acetate (150 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (5×150 mL) and with dichloromethane (5×100 mL)
  5. dry with materialThe combined organic phase was dried (Na2SO4), solvent
  6. customevaporated in vacuo
  7. customthe resulting residue purified by chromatography on silica gel with a gradient of methanol:dichloromethane (1:19
  8. customThe resultant solid was recrystallised from diethyl ether

出典と根拠

ORDレコード
ord-bb0882a78b2349719869f1e47b983b74
出典データセット
uspto-grants-2010_10
特許番号
US07807686B2

反応ノート

読み込み中…