Dimethylamine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-dimethylaminomethyl-pyrazin-2-yl)-propionamide

HRID 719907Notes

Reaction equation

HRID 719907 reaction equation
Br[CH2:2][C:3]1[N:4]=[CH:5][C:6]([NH:9][C:10](=[O:29])[C@@H:11]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[C:20]([Cl:28])[CH:19]=2)[CH2:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[N:7][CH:8]=1.[CH3:30][NH:31][CH3:32]>O1CCCC1>[Cl:28][C:20]1[CH:19]=[C:18]([C@@H:11]([CH2:12][CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17]2)[C:10]([NH:9][C:6]2[CH:5]=[N:4][C:3]([CH2:2][N:31]([CH3:32])[CH3:30])=[CH:8][N:7]=2)=[O:29])[CH:23]=[CH:22][C:21]=1[S:24]([CH3:27])(=[O:26])=[O:25]

Participants

4

Reactant 2

HCID 674Dimethylamine3×HCID 67482634N-(5-bromomethyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Product 1

HCID 509085692(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-dimethylaminomethyl-pyrazin-2-yl)-propionamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
0 °C

Procedure

A solution of N-(5-bromomethyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (prepared as in Example 30, 138.5 mg, 0.28 mmol) in tetrahydrofuran (2.6 mL) was cooled to 0° C. and then was treated with a 2.0M solution of dimethylamine in tetrahydrofuran (275 μL, 0.55 mmol). The reaction was stirred at 0° C. for 30 min and then at 25° C. for 1 h. A second aliquot of a 2.0M solution of dimethylamine in tetrahydrofuran (275 μL, 0.55 mmol) was added, and the reaction was stirred at 25° C. for 1 h. A third aliquot of a 2.0M solution of dimethylamine in tetrahydrofuran (138 μL, 0.28 mmol) was added, and the reaction was stirred at 25° C. for 1.5 h, at which point, APCI-LRMS indicated the reaction had gone to completion. The reaction was concentrated in vacuo and then was diluted with ethyl acetate (50 mL), washed with water (25 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 100% methanol) afforded impure 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-dimethylaminomethyl-pyrazin-2-yl)-propionamide as an orange oil. This impure product was re-purified by reverse phase high-performance liquid chromatography (Waters symmetry packing, acetonitrile/water with 0.05% trifluoroacetic acid, 2% to 45% acetonitrile gradient). The fractions containing product were concentrated in vacuo to afford 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-dimethylaminomethyl-pyrazin-2-yl)-propionamide (50.4 mg, 39%) as a light yellow foam: mp 88.0–91.5° C. (foam to gel); (ES)+-HRMS m/e calcd for C22H29ClN4O3S (M+H)+ 465.1722, found 465.1726.

Workup

  1. waitat 25° C. for 1 h
  2. stirringthe reaction was stirred at 25° C. for 1 h
  3. stirringthe reaction was stirred at 25° C. for 1.5 h, at which point, APCI-LRMS
  4. concentrationThe reaction was concentrated in vacuo
  5. additionwas diluted with ethyl acetate (50 mL)
  6. washwashed with water (25 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2564f4ecf8fe485ea5db8b97a17bc775
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

Loading…