Pyrrolidine → HCID 178420445, compound

HRID 1241513Notes

Reaction equation

HRID 1241513 reaction equation
[N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([C@H:13]3[CH2:16][C@H:15]([CH2:17]OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:14]3)=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1>CC(N(C)C)=O>[N:1]1([CH2:6][C:7]2[CH:8]=[CH:9][C:10]([C@H:13]3[CH2:14][C@H:15]([CH2:17][N:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)[CH2:16]3)=[CH:11][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 178427760HCID 178427760, compound

Product 1

HCID 178420445HCID 178420445, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirring solution of Example 48 (trans-toluene-4-sulfonic acid 3-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethyl ester) (200 mg, 0.5 mmol) in DMA (1.5 mL) was added the appropriate amine, for example pyrollidine (84 uL, 1.0 mmol). The reaction was then heated to 110 □C (oil bath). After 12 hr the reaction was cooled to rt and concentrated under reduced pressure. This material was free based by stirring in solid K2CO3 and MeOH for 2 hours. After 2 hr of stirring silica gel was added to the vessel (dry pack) and the methanolic slurry was concentrated. Purfication of this material was accomplished by flash column chromatography using a 12 g ISCO column, eluting with a gradient of 5%–10% MeOH/CH2Cl2 with 0.2% NH4OH. The product containing fractions were collected and concentrated to give the title compound as a colorless oil. The HCl salt was made by taken the freebase up in EtOAc and then adding a solution of HCl (2 eq, 1 M HCl, THF) to give a colorless solid.

Workup

  1. temperatureThe reaction was then heated to 110 □C (oil bath)
  2. concentrationconcentrated under reduced pressure
  3. additionAfter 2 hr of stirring silica gel was added to the vessel (dry pack)
  4. concentrationthe methanolic slurry was concentrated
  5. washeluting with a gradient of 5%–10% MeOH/CH2Cl2 with 0.2% NH4OH
  6. additionThe product containing fractions
  7. customwere collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-bda4a1085bdf40e18cbf1ed1e268b7fa
Source dataset
uspto-grants-2006_10
Patent number
US07115600B2

Reaction notes

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