4-Hydroxypyrrolidine → N-{[2-(3-hydroxypyrrolidin-1-yl)-2-oxoethyl](oxido)phenyl--sulfanylidene}-5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)nicotinamide

HRID 607469Notes

Reaction equation

HRID 607469 reaction equation
C([C@H:3]([S:7]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)(=[N:9][C:10]([C:12]1[CH:13]=[N:14][CH:15]=[C:16]([C:18]#[C:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([NH:26][C:27]([C:29]3[O:30][CH:31]=[CH:32][C:33]=3[CH3:34])=[O:28])[CH:21]=2)[CH:17]=1)=[O:11])=[O:8])[C:4]([O-:6])=O)C.[NH:41]1[CH2:45][CH2:44][CH:43]([OH:46])[CH2:42]1>C1COCC1>[OH:46][CH:43]1[CH2:44][CH2:45][N:41]([C:4](=[O:6])[CH2:3][S:7](=[O:8])([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)=[N:9][C:10](=[O:11])[C:12]2[CH:17]=[C:16]([C:18]#[C:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([NH:26][C:27]([C:29]4[O:30][CH:31]=[CH:32][C:33]=4[CH3:34])=[O:28])[CH:21]=3)[CH:15]=[N:14][CH:13]=2)[CH2:42]1

Participants

4

Reactant 2

HCID 982104-HydroxypyrrolidineHCID 86629488(S)-ethyl(N-{[5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}-S-phenylsulfonimidoyl)acetate

Product 1

HCID 57657922N-{[2-(3-hydroxypyrrolidin-1-yl)-2-oxoethyl](oxido)phenyl--sulfanylidene}-5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)nicotinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To the solution of (S)-ethyl(N-{[5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}-S-phenylsulfonimidoyl)acetate (4.03 g, 7.26 mmol) in anhydrous THF (75 mL) was added dropwise 3-pyrrolidinol (6.0 mL) and the resulting reaction solution was heated at 65° C. for 5 hours. The reaction was then concentrated under reduced pressure and the yellow oily residue was partitioned between aqueous NH4Cl and EtOAc. The organic layer was separated and washed sequentially with brine (1×), saturated aqueous NaHCO3 (1×), brine (1×), and finally dried with anhydrous sodium sulfate overnight. The clear solution was decanted and concentrated. The oily residue was subject to multiple times of column chromatography (eg. from CH2Cl2 to MeOH—CH2Cl2 1:25 or from EtOAc-Hex 3:1 to MeOH-EtOAc 1:100) the title compound as white foam (2.35 g, 54%).

Workup

  1. customthe resulting reaction solution
  2. concentrationThe reaction was then concentrated under reduced pressure
  3. customthe yellow oily residue was partitioned between aqueous NH4Cl and EtOAc
  4. customThe organic layer was separated
  5. washwashed sequentially with brine (1×), saturated aqueous NaHCO3 (1×), brine (1×)
  6. dry with materialfinally dried with anhydrous sodium sulfate overnight
  7. customThe clear solution was decanted
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-dc23f62be93d49b3a45a19acd50d3104
Source dataset
uspto-grants-2011_03
Patent number
US07915443B2

Reaction notes

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