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

HRID 1838011Notes

Reaction equation

HRID 1838011 reaction equation
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

Participants

7

Reactant 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

Product 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-oneYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(±)-(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.

Workup

  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)

Sources & evidence

ORD record
ord-af96a26144204859ab3f3300a7dd8e2c
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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