Dichloromethane → HCID 58557342, compound

HRID 1969601Notes

Reaction equation

HRID 1969601 reaction equation
[NH:1]1[CH2:5][CH2:4][C@@H:3]([CH2:6][C:7]2[N:11]3[C:12]4[CH:18]=[CH:17][N:16]([S:19]([C:22]5[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=5)(=[O:21])=[O:20])[C:13]=4[N:14]=[CH:15][C:10]3=[N:9][N:8]=2)[CH2:2]1.Cl[C:30]1[CH:35]=[N:34][C:33]([C:36]#[N:37])=[CH:32][N:31]=1.CCN(C(C)C)C(C)C.C(Cl)Cl>C(O)CC>[S:19]([N:16]1[C:13]2[N:14]=[CH:15][C:10]3[N:11]([C:7]([CH2:6][C@@H:3]4[CH2:4][CH2:5][N:1]([C:30]5[N:31]=[CH:32][C:33]([C:36]#[N:37])=[N:34][CH:35]=5)[CH2:2]4)=[N:8][N:9]=3)[C:12]=2[CH:18]=[CH:17]1)([C:22]1[CH:23]=[CH:24][C:25]([CH3:26])=[CH:27][CH:28]=1)(=[O:21])=[O:20]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 122957285-Chloropyrazine-2-carbonitrileHCID 58557454HCID 58557454, compound

Product 1

HCID 58557342HCID 58557342, compoundYield 27.7%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of (S)-1-(pyrrolidin-3-ylmethyl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.160 g, 0.404 mmol, prepared using B from Preparation #A.1 and E with HCl), 2-chloro-5-cyanopyrazine (0.084 g, 0.60 mmol, ArkPharm) and DIEA (0.28 mL, 1.6 mmol) in n-PrOH (2.0 mL) was heated in a CEM microwave at about 150° C. for about 30 min (250 psi maximum pressure, 10 min maximum ramp, 200 maximum watts). The reaction mixture was cooled to ambient temperature and DCM (20 mL) was added. The solution was washed with water (20 mL) and brine (20 mL). The organic layer was separated, dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The residue was taken up in DCM (10 mL), adsorbed onto silica gel (1 g), and purified by silica gel chromatography eluting with 100% EtOAc to give a pink solid. The material was triturated with a mixture of EtOAc (10 mL) and 10% MeOH in DCM (10 mL). The insoluble material was collected by filtration to give (S)-5-(3-((6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)methyl)pyrrolidin-1-yl)pyrazine-2-carbonitrile as an off-white solid (0.056 g, 27%): LC/MS (Table 1, Method c) Rt=1.34 min; MS m/z: 500 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. washThe solution was washed with water (20 mL) and brine (20 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. custompurified by silica gel chromatography
  7. washeluting with 100% EtOAc
  8. customto give a pink solid
  9. customThe material was triturated with a mixture of EtOAc (10 mL) and 10% MeOH in DCM (10 mL)
  10. filtrationThe insoluble material was collected by filtration

Sources & evidence

ORD record
ord-8d32797830cb493c927cfd6ce0a6a9e6
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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