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

HRID 1838011노트

반응식

HRID 1838011 반응식
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

참가 물질

7

반응물 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

생성물 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-one수율 55%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

(±)-(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.

후처리

  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)

출처 및 근거

ORD 기록
ord-af96a26144204859ab3f3300a7dd8e2c
출처 데이터셋
uspto-grants-2004_08
특허 번호
US06784167B2

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