Azetidine-1-sulfonyl chloride → N-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)-cyclopentyl)azetidine-1-sulfonamide

HRID 1969621Notes

Reaction equation

HRID 1969621 reaction equation
[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17]([S:20]([C:23]5[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=5)(=[O:22])=[O:21])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH2:30])[CH2:4]1)[CH3:2].[N:31]1([S:35](Cl)(=[O:37])=[O:36])[CH2:34][CH2:33][CH2:32]1>CN(C=O)C>[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17]([S:20]([C:23]5[CH:24]=[CH:25][C:26]([CH3:27])=[CH:28][CH:29]=5)(=[O:22])=[O:21])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH:30][S:35]([N:31]2[CH2:34][CH2:33][CH2:32]2)(=[O:37])=[O:36])[CH2:4]1)[CH3:2]

Participants

4

Reactant 2

HCID 55280383Azetidine-1-sulfonyl chlorideHCID 58557840(1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine

Product 1

HCID 58557909N-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)-cyclopentyl)azetidine-1-sulfonamideYield 78.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A flask was charged with (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine (0.200 g, 0.471 mmol, Example #8, Step M) and DMF (4 mL). The solution was cooled to about 0° C. followed by the addition of TEA (0.16 mL, 1.2 mmol) and azetidine-1-sulfonyl chloride (0.165 g, 1.06 mmol, Preparation #CC.1). The reaction mixture was warmed to ambient temperature and was stirred for about 2 h. The solvent was removed under reduced pressure and DCM (10 mL) was added to the resulting residue. The organic solution was washed with water and brine (5 mL each). The combined organics were dried over anhydrous MgSO4, filtered, and concd under reduced pressure to give a brown oil. The crude material was purified by silica gel chromatography eluting with a gradient of 0-70% EtOAc in DCM to afford N-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)-cyclopentyl)azetidine-1-sulfonamide (0.20 g, 77%) as a white solid: LC/MS (Table 1, Method a) Rt=2.39 min; MS m/z: 544 (M+H)+.

Workup

  1. temperatureThe reaction mixture was warmed to ambient temperature
  2. customThe solvent was removed under reduced pressure and DCM (10 mL)
  3. additionwas added to the resulting residue
  4. washThe organic solution was washed with water and brine (5 mL each)
  5. dry with materialThe combined organics were dried over anhydrous MgSO4
  6. filtrationfiltered
  7. customconcd under reduced pressure to give a brown oil
  8. customThe crude material was purified by silica gel chromatography
  9. washeluting with a gradient of 0-70% EtOAc in DCM

Sources & evidence

ORD record
ord-129fd2de768541c19d2d139f6028c96f
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

Loading…