Hydrochloric Acid → (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine

HRID 1969620Notes

Reaction equation

HRID 1969620 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]([NH:30]C(=O)C)[CH2:4]1)[CH3:2].Cl>O1CCOCC1>[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]([NH2:30])[CH2:4]1)[CH3:2]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 58557700N-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)acetamide

Product 1

HCID 58557840(1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamineYield 56%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 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)acetamide (6.0 g, 12.86 mmol, Example #8, Step L) in 1,4-dioxane (78 mL) was added aqueous HCl (6 N, 75 mL, 450 mmol). The reaction mixture was heated at about 95° C. for about 16 h. The reaction was cooled to ambient temperature and the solvent was removed under reduced pressure. The residue was diluted with DCM (50 mL) and washed with saturated aqueous NaHCO3 (100 mL). The aqueous portion was extracted with additional DCM (3×50 mL) and the combined organic layers were dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-100% DCM/MeOH/NH4OH (950:45:5) in DCM to give (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine (3.05 g, 56%) as a tan solid: LC/MS (Table 1, Method a) Rt=1.85 min; MS m/z: 425 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customthe solvent was removed under reduced pressure
  3. additionThe residue was diluted with DCM (50 mL)
  4. washwashed with saturated aqueous NaHCO3 (100 mL)
  5. extractionThe aqueous portion was extracted with additional DCM (3×50 mL)
  6. dry with materialthe combined organic layers were dried over anhydrous MgSO4
  7. filtrationfiltered
  8. customThe crude material was purified by silica gel chromatography
  9. washeluting with a gradient of 0-100% DCM/MeOH/NH4OH (950:45:5) in DCM

Sources & evidence

ORD record
ord-aaf1d910264c4f85a0c11bcbbe5be9d7
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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