2,5-Dimethoxytetrahydrofuran → 1-((1R,35)-3-(1H-pyrrol-1-yl)cyclopentyl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine

HRID 1969508Notes

Reaction equation

HRID 1969508 reaction equation
CO[CH:3]1[CH2:7][CH2:6][CH:5](OC)O1.Cl.[S:11]([N:21]1[C:25]2[N:26]=[CH:27][C:28]3[N:29]([C:30]([C@@H:33]4[CH2:37][CH2:36][C@H:35]([NH2:38])[CH2:34]4)=[N:31][N:32]=3)[C:24]=2[CH:23]=[CH:22]1)([C:14]1[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=1)(=[O:13])=[O:12].CC([O-])=O.[Na+]>O.C(Cl)Cl>[N:38]1([C@H:35]2[CH2:36][CH2:37][C@@H:33]([C:30]3[N:29]4[C:24]5[CH:23]=[CH:22][N:21]([S:11]([C:14]6[CH:15]=[CH:16][C:17]([CH3:18])=[CH:19][CH:20]=6)(=[O:13])=[O:12])[C:25]=5[N:26]=[CH:27][C:28]4=[N:32][N:31]=3)[CH2:34]2)[CH:3]=[CH:7][CH:6]=[CH:5]1

Participants

6

Reactant 3

HCID 790982,5-Dimethoxytetrahydrofuran3×HCID 517045Sodium AcetateHCID 69014326(1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine hydrochloride

Product 1

HCID 679979791-((1R,35)-3-(1H-pyrrol-1-yl)cyclopentyl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazineYield 101.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2,5-dimethoxytetrahydrofuran (0.14 g, 1.1 mmol) in water (3 mL) was heated at about 100° C. for about 1.5 h. The solution was cooled to ambient temperature. A suspension of (1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclo-pentanamine hydro-chloride (0.10 g, 0.21 mmol, prepared using E from Preparation #B.1 and HCl) and NaOAc (0.05 g, 0.61 mmol) in DCM (5 mL) was added to the aqueous solution. The reaction mixture was stirred at ambient temperature for about 1 h followed by addition of additional 2,5-dimethoxytetrahydrofuran (0.14 g, 1.1 mmol). The reaction mixture was heated to about 40° C. for about 15 h. Additional 2,5-dimethoxytetrahydrofuran (0.14 g, 1.1 mmol) was added and the reaction mixture was stirred at about 40° C. for about 8 h then at about 35° C. for about 48 h. The reaction was diluted with DCM (10 mL) and water (10 mL). The layers were separated and the organic layer was washed with water (2×10 mL) and brine (10 mL), dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure to give 1-((1R,3S)-3-(1H-pyrrol-1-yl)cyclopentyl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.095 g, 99%) as a yellow residue: LC/MS (Table 1, Method a) Rt=2.42 min; MS m/z: 447 (M+H)+.

Workup

  1. additionwas added to the aqueous solution
  2. temperatureThe reaction mixture was heated to about 40° C. for about 15 h
  3. stirringthe reaction mixture was stirred at about 40° C. for about 8 h
  4. waitat about 35° C. for about 48 h
  5. customThe layers were separated
  6. washthe organic layer was washed with water (2×10 mL) and brine (10 mL)
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-8a503cd764e2414abf927cc8ac856c45
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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