Sodium Acetate → 1-((1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)-1H-pyrrole-3-carbaldehyde

HRID 1969509Notes

Reaction equation

HRID 1969509 reaction equation
Cl.[S:2]([N:12]1[C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([C@@H:24]4[CH2:28][CH2:27][C@H:26]([NH2:29])[CH2:25]4)=[N:22][N:23]=3)[C:15]=2[CH:14]=[CH:13]1)([C:5]1[CH:11]=[CH:10][C:8]([CH3:9])=[CH:7][CH:6]=1)(=[O:4])=[O:3].CC([O-])=O.[Na+].C[O:36][CH:37]1[CH:41]([CH:42]=O)[CH2:40][CH:39](OC)O1>C(Cl)Cl.O>[S:2]([N:12]1[C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([C@@H:24]4[CH2:28][CH2:27][C@H:26]([N:29]5[CH:39]=[CH:40][C:41]([CH:37]=[O:36])=[CH:42]5)[CH2:25]4)=[N:22][N:23]=3)[C:15]=2[CH:14]=[CH:13]1)([C:5]1[CH:11]=[CH:10][C:8]([CH3:9])=[CH:7][CH:6]=1)(=[O:4])=[O:3]

Participants

6

Reactant 3

HCID 517045Sodium AcetateHCID 567310Tetrahydro-2,5-dimethoxyfuran-3-carbaldehydeHCID 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 866604291-((1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)-1H-pyrrole-3-carbaldehydeYield 33.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

To a suspension of (1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine hydrochloride (0.175 g, 0.373 mmol, prepared using E from Preparation #B.1 and HCl) and NaOAc (0.100 g, 1.22 mmol) in DCM (3 mL) and water (2 mL) was added 2,5-dimethoxytetrahydrofuran-3-carbaldehyde (0.600 g, 3.37 mmol). The reaction was heated to about 40° C. for about 24 h. The reaction mixture was diluted with DCM (30 mL) and washed with water (4×20 mL). The organic layer was dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure to give a brown residue. The crude material was purified by flash chromatography on silica gel eluting with a gradient of 20-100% EtOAc in DCM to give 1-((1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)-1H-pyrrole-3-carbaldehyde (0.059 g, 33%) as a yellow amorphous solid: LC/MS (Table 1, Method a) Rt=2.10 min; MS m/z: 475 (M+H)+.

Workup

  1. washwashed with water (4×20 mL)
  2. dry with materialThe organic layer was dried over anhydrous MgSO4
  3. filtrationfiltered
  4. customthe solvent was removed under reduced pressure
  5. customto give a brown residue
  6. customThe crude material was purified by flash chromatography on silica gel eluting with a gradient of 20-100% EtOAc in DCM

Sources & evidence

ORD record
ord-44bec548043f4575acbe7b2d24a2a9bf
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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