Potassium Carbonate → 4-Methyl-3-[3-[[1-methyl-1-[2-[2-[methyl[(phenylmethoxy)carbonyl]amino]ethoxy]phenyl]ethyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzoic acid methyl ester

HRID 1697334ノート

反応式

HRID 1697334 の反応式
[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[OH:27])([CH3:20])[CH3:19])[C:12]2=[O:28])[CH:5]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:37][CH2:38][N:39]([CH3:50])[C:40](=[O:49])[O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C(#N)C>[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]([CH3:20])([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH2:37][CH2:38][N:39]([CH3:50])[C:40]([O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[O:49])[CH3:19])[C:12]2=[O:28])[CH:5]=1

参加物

5

反応物 3

HCID 11430Potassium Carbonate2 回HCID 13592063Benzyl (2-chloroethyl)methylcarbamate2 回HCID 666901483-[3-[[1-(2-Hydroxyphenyl)-1-methylethyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid methyl ester

生成物 1

HCID 666901444-Methyl-3-[3-[[1-methyl-1-[2-[2-[methyl[(phenylmethoxy)carbonyl]amino]ethoxy]phenyl]ethyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzoic acid methyl ester収率 53.1%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
85 °C

実験手順

To 3-[3-[[1-(2-Hydroxyphenyl)-1-methylethyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid methyl ester (Example 220b, 2.495 g) in acetonitrile (150 mL) was added potassium carbonate (1.753 g) followed by benzyl 2-chloroethyl(methyl)carbamate (J. Med. Chem., 1992, 35 (17), 3246, 1.660 g) and the reaction heated at 85° C. for 72 h under nitrogen. Further benzyl 2-chloroethyl(methyl)carbamate (0.58 g) and potassium carbonate (0.35 g) were added and the reaction stirred for 2 days. The reaction mixture was cooled, evaporated to dryness and the residue partitioned between water and dichloromethane and the organic layer separated. The aqueous was further extracted with dichloromethane (2×) and the combined organics dried (Na2SO4) and evaporated. Purification (SiO2 chromatography eluting with 40-100% ethyl acetate) gave the subtitle product (1.97 g).

後処理

  1. temperatureThe reaction mixture was cooled
  2. customevaporated to dryness
  3. customthe residue partitioned between water and dichloromethane
  4. customthe organic layer separated
  5. extractionThe aqueous was further extracted with dichloromethane (2×)
  6. dry with materialthe combined organics dried (Na2SO4)
  7. customevaporated
  8. customPurification (SiO2 chromatography eluting with 40-100% ethyl acetate)

出典と根拠

ORDレコード
ord-24e1435c38704e60ae7995223741ae77
出典データセット
uspto-grants-2012_04
特許番号
US08163905B2

反応ノート

読み込み中…