Pyrrolidine → HCID 24953409, compound

HRID 1801583Notes

Reaction equation

HRID 1801583 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[C:10]([CH2:12][NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[CH:9]=[CH:8][C:7]=1[Cl:22])=[O:4].[NH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1>C1COCC1>[Cl:22][C:7]1[CH:8]=[CH:9][C:10]([CH2:12][NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])=[CH:11][C:6]=1[NH:5][C:3](=[O:4])[CH2:2][N:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 24952342HCID 24952342, compound

Product 1

HCID 24953409HCID 24953409, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (R)-2-chloro-N-(2-chloro-5-((1-phenylethylamino)methyl)phenyl)acetamide 46 (0.397 g, 1.2 mmol) in THF (6 mL) was added pyrrolidine (3.0 mL, 36 mmol). The reaction mixture was heated to 50° C. for 30 min, cooled to room temperature, partially concentrated under reduced pressure, quenched with saturated NaHCO3, and diluted with EtOAc. The aqueous phase was extracted with EtOAc (3×) and the combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 1% to 10% MeOH in DCM) gave (R)—N-(2-chloro-5-((1-phenylethylamino)methyl)phenyl)-2-(pyrrolidin-1-yl)acetamide 47 (0.292 g, 67% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 1.36 (d, J=6.5 Hz, 3H), 1.83-1.91 (m, 4H), 2.68-2.79 (m, 4H), 3.33 (s, 2H), 3.58 (d, J=13.5 Hz, 1H), 3.64 (d, J=13.3 Hz, 1H), 3.81 (q, J=6.7 Hz, 1H), 6.98 (d, J=8.2 Hz, 1H), 7.23-7.37 (m, 7H), 8.38 (s, 1H), 9.93 (s, 1H). Mass spectrum: calculated for C21H26ClN3O 371.2. found 372.2 (M++1).

Workup

  1. temperaturecooled to room temperature
  2. concentrationpartially concentrated under reduced pressure
  3. customquenched with saturated NaHCO3
  4. additiondiluted with EtOAc
  5. extractionThe aqueous phase was extracted with EtOAc (3×)
  6. washthe combined organic extracts were washed with brine (1×)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by flash column chromatography on silica gel (eluted with 1% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-a98d4cb97db94ac1a084ba3fa2f01d06
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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