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

HRID 1969917Notes

Reaction equation

HRID 1969917 reaction equation
[Si]([O:8][C@H:9]1[CH2:13][C@H:12]([C:14]2[N:18]3[C:19]4[CH:25]=[CH:24][N:23]([S:26]([C:29]5[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=5)(=[O:28])=[O:27])[C:20]=4[N:21]=[CH:22][C:17]3=[N:16][N:15]=2)[C@H:11]([CH2:36][CH3:37])[CH2:10]1)(C(C)(C)C)(C)C.Cl.CCOC(C)=O>C(O)C.C([C@H]1[C@@H](C2N3C4C=CN(S(C5C=CC(C)=CC=5)(=O)=O)C=4N=CC3=NN=2)C[C@H](O)C1)C>[CH2:36]([CH:11]1[CH:12]([C:14]2[N:18]3[C:19]4[CH:25]=[CH:24][N:23]([S:26]([C:29]5[CH:30]=[CH:31][C:32]([CH3:33])=[CH:34][CH:35]=5)(=[O:28])=[O:27])[C:20]=4[N:21]=[CH:22][C:17]3=[N:16][N:15]=2)[CH2:13][CH:9]([OH:8])[CH2:10]1)[CH3:37]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 67999559HCID 67999559, compound

Product 1

HCID 585575563-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 67998454HCID 67998454, compoundSolvent

Procedure

A scalemic mixture enriched in 1-((1S,2R,4R)-4-(tert-butyldimethylsilyloxy)-2-ethylcyclopentyl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (1.55 g, 2.87 mmol) was suspended in ethanol (30 mL). Concentrated HCl (0.3 mL, 3.65 mmol) was added dropwise. After about 1 h., the suspension was sonicated until all solid went into solution. EtOAc (250 mL) was added and the organics were washed with saturated aqueous NaHCO3 (2×30 mL) and brine (30 mL), dried over anhydrous MgSO4, filtered, and concd under reduce pressure. The residue was purified using silica gel chromatography eluting with 30-80% EtOAc in DCM to give a scalemic mixture enriched in (1R,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol (1.09 g, 90%): LC/MS (Table 1, Method b) Rt=1.99 min; MS m/z: 426 (M+H)+.

Workup

  1. customthe suspension was sonicated until all solid
  2. washthe organics were washed with saturated aqueous NaHCO3 (2×30 mL) and brine (30 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. customThe residue was purified
  6. washeluting with 30-80% EtOAc in DCM
  7. customto give a scalemic mixture

Sources & evidence

ORD record
ord-3d6c02ecc327454c95bb3388a956a7c7
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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