Potassium Carbonate → (S)-3-(7-Chloro-isoquinolin-6-ylsulfanyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 404736Notes

Reaction equation

HRID 404736 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([S:13][C:14](=O)[CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].FC1C=[C:26]2[C:31](=[CH:32][C:33]=1[Cl:34])[CH:30]=[N:29][CH:28]=[CH:27]2.C1CCN2C(=NCCC2)CC1>CO>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([S:13][C:14]2[CH:15]=[C:26]3[C:31](=[CH:32][C:33]=2[Cl:34])[CH:30]=[N:29][CH:28]=[CH:27]3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 534189227-Chloro-6-fluoroisoquinolineHCID 59560788Tert-butyl (S)-3-(acetylthio)pyrrolidine-1-carboxylate

Product 1

HCID 59290650(S)-3-(7-Chloro-isoquinolin-6-ylsulfanyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 86.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3.5 g (14.2 mmol) (S)-3-Acetylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester (266) were dissolved in 95 ml MeOH and treated with 2.34 g (16.9 mmol) potassium carbonate and stirred over night. After evaporation of all volatiles the residue was taken up in 60 ml of degassed DMF, 1.27 g (15 mmol) 6-Fluoro-7-chloroisoquinoline and 2.25 ml (15 mmol) DBU were added. After 3 h at RRT the mixture was concentrated, taken up in ethyl acetate and washed with brine. The organic phases were dried over Sodium sulfate and evaporated. Purification over silica gel (10% to 40% ethyl acetate in heptane) gave 4.5 g of the expected compound.

Workup

  1. customAfter evaporation of all volatiles the residue
  2. concentrationAfter 3 h at RRT the mixture was concentrated
  3. washwashed with brine
  4. dry with materialThe organic phases were dried over Sodium sulfate
  5. customevaporated
  6. customPurification over silica gel (10% to 40% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-9dcf45fa79544affa2fdb1f99b93758a
Source dataset
uspto-grants-2014_06
Patent number
US08748614B2

Reaction notes

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