Dimethylamine → (2R)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N,N-dimethylethanamide

HRID 2108702

反応式

HRID 2108702 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([N:13]1[C@H:18]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:17](=[O:23])[NH:16][C@H:15]([CH:24]2[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:25]2)[C:14]1=[O:33])[C:10]([OH:12])=O.[CH2:34]1[N:39](P(Cl)(N2C(=O)OCC2)=O)[C:37](=O)OC1.C(N(CC)CC)C.CNC>ClCCl.C(#N)C.O1CCCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([N:13]1[C@H:18]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:17](=[O:23])[NH:16][C@H:15]([CH:24]2[CH2:25][C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:32]2)[C:14]1=[O:33])[C:10]([N:39]([CH3:34])[CH3:37])=[O:12]

参加物

7

反応物 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chloride3 回HCID 68844874(2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-ethanoic acid

生成物 1

HCID 11465834(2R)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N,N-dimethylethanamide

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 21877088Acetonitrile methylene chloride溶媒2 回

実験手順

The acid (2RS)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-ethanoic acid (0.747 g) prepared as described above was dried over P4O10 in vacuo for five hours to give 0.724 g drier material; this was dissolved in anhydrous dichloromethane:acetonitrile (1:1 v/v, 6 ml) and treated with triethylanne (0.223 ml) and BOP-Cl (bis(2-oxo-3-oxazolidinyl)phosphinic chloride, dissolved in anhydrous dichloromethane:acetonitrile (1:1 v/v, 6 ml) and treated with triethylamine (0.223 ml) and BOP-Cl (bis(2-oxo-3-oxazolidinyl)phosphinic chloride, 0.450 g) and the mixture was sonicated for ca. 1 min to give a gelatinous mass. After 10 minutes at room temperature a solution of dimethylamine in tetrahydrofuran (10 ml of 2M solution) was added to give a clear solution; this was left for 16 hours at room temperature. The solvents were removed under reduced pressure and the mixture was partitioned beween dichloromethane and 0.1M hydrochloric acid. The organic phase was separated (hydrophobic frit) and evaporated under reduced pressure. The crude product was purified by flash column chromatography (12 g Biotage™ silica cartridge eluted with (i) 1:1 ethyl acetate:cyclohexane (ii) ethyl acetate (iii) ethyl acetate:methanol 9:1) to give the (2R)-2-(2,4-difluorophenyl)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N,N-dimethylethanamide as a colourless solid 0.285 g.

後処理

  1. dry with materialabove was dried over P4O10 in vacuo for five hours
  2. customto give 0.724 g drier material
  3. customthe mixture was sonicated for ca. 1 min
  4. customto give a gelatinous mass
  5. customto give a clear solution
  6. customThe solvents were removed under reduced pressure
  7. customthe mixture was partitioned
  8. customThe organic phase was separated (hydrophobic frit)
  9. customevaporated under reduced pressure
  10. customThe crude product was purified by flash column chromatography (12 g Biotage™ silica cartridge eluted with (i) 1:1 ethyl acetate:cyclohexane (ii) ethyl acetate (iii) ethyl acetate:methanol 9:1)

出典と根拠

ORDレコード
ord-cd3955304f824af896d8a3b7287e3bf2
出典データセット
uspto-grants-2009_04
特許番号
US07514437B2

関連ノート

読み込み中…