Water → (+/-)-(4R*,5R*)-5-{1(1S*)[5-(3-{[(4-fluorophenyl)amino]carbonylamino}phenyl)(2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-one

HRID 1838011ノート

反応式

HRID 1838011 の反応式
Br[C:2]1[S:6][C:5]([C@@H:7]([OH:21])[C@@H:8]2[N:12]([CH3:13])[C:11](=[O:14])[CH2:10][C@@H:9]2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:4][CH:3]=1.[NH2:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1.[F:32][C:33]1[CH:38]=[CH:37][C:36]([N:39]=[C:40]=[O:41])=[CH:35][CH:34]=1.O>C1COCC1>[NH2:22][C:23]1[CH:28]=[C:27]([C:2]2[S:6][C:5]([C@@H:7]([OH:21])[C@@H:8]3[N:12]([CH3:13])[C:11](=[O:14])[CH2:10][C@@H:9]3[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:4][CH:3]=2)[CH:26]=[CH:25][CH:24]=1.[F:32][C:33]1[CH:38]=[CH:37][C:36]([NH:39][C:40]([NH:22][C:23]2[CH:28]=[C:27]([C:2]3[S:6][C:5]([C@@H:7]([OH:21])[C@@H:8]4[N:12]([CH3:13])[C:11](=[O:14])[CH2:10][C@@H:9]4[C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)=[CH:4][CH:3]=3)[CH:26]=[CH:25][CH:24]=2)=[O:41])=[CH:35][CH:34]=1

参加物

7

反応物 4

HCID 962WaterHCID 709554-Fluorophenyl isocyanateHCID 922693-Aminophenylboronic acidHCID 69891005(4R*,5R*)-5-[(1S*)(5-bromo(2-thienyl))hydroxymethyl]-1-methyl-4-phenylpyrrolidin-2-one

生成物 2

HCID 9969932(+/-)-(4R*,5R*)-5-{(1S*) [5-(3-aminophenyl) (2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-oneHCID 59066489(+/-)-(4R*,5R*)-5-{1(1S*)[5-(3-{[(4-fluorophenyl)amino]carbonylamino}phenyl)(2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-one収率 55%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

(±)-(4R*,5R*)-5-{(1S*) [5-(3-aminophenyl) (2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-one was prepared from (±)-(4R*,5R*)-5-[(1S*)(5-bromo(2-thienyl))hydroxymethyl]-1-methyl-4-phenylpyrrolidin-2-one (Example 5, step 2) and 3-aminophenylboronic acid, using a procedure analogous to that described for Examples 5, step 3. A mixture of the resulting compound (0.2 g, 0.53 mmol) and 4-fluorophenylisocyanate (0.073 g, 0.53 mmol) in THF (5 mL) were heated at the reflux temperature for 4 h. The resulting mixture was treated with water and extracted with CH2Cl2. The organic layers were dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography (EtOAc) to give (±)-(4R*,5R*)-5-{1(1S*)[5-(3-{[(4-fluorophenyl)amino]carbonylamino}phenyl)(2-thienyl)]hydroxymethyl}-1-methyl-4-phenylpyrrolidin-2-one (0.15 g, 55%) as an off-white solid: mp: 181° C.; TLC (EtOAc) Rf 0.26.

後処理

  1. temperaturewere heated at the reflux temperature for 4 h
  2. extractionextracted with CH2Cl2
  3. dry with materialThe organic layers were dried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by flash chromatography (EtOAc)

出典と根拠

ORDレコード
ord-af96a26144204859ab3f3300a7dd8e2c
出典データセット
uspto-grants-2004_08
特許番号
US06784167B2

反応ノート

読み込み中…