Sodium hydride → 2-Chloro-6-[4-(3-[2-(2,2,2-trifluoroethyl)guanidino]pyrazol-1-yl)butoxy]pyrazine

HRID 1463064Notes

Reaction equation

HRID 1463064 reaction equation
[H-].[Na+].[OH:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14]([NH2:21])=[N:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[N:9]1.[Cl:22][C:23]1[CH:28]=[N:27][CH:26]=[C:25](Cl)[N:24]=1>C(O)(C)(C)C>[Cl:22][C:23]1[CH:28]=[N:27][CH:26]=[C:25]([O:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([NH2:21])=[N:15][CH2:16][C:17]([F:20])([F:18])[F:19])=[N:9]2)[N:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 785042,6-DichloropyrazineHCID 204513041-(4-Hydroxybutyl)-3-[2-(2,2,2-trifluoroethyl)guanidino]pyrazole

Product 1

HCID 204513112-Chloro-6-[4-(3-[2-(2,2,2-trifluoroethyl)guanidino]pyrazol-1-yl)butoxy]pyrazineYield 43.4%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

Sodium hydride (46 mg. of a 61% w/w dispersion in oil) was added to a hot solution of 1-(4-hydroxybutyl)-3-[2-(2,2,2-trifluoroethyl)guanidino]pyrazole (279 mg.) in dry t-butanol (10 ml.). 2,6-Dichloropyrazine (180 mg.) was added and the mixture was stirred at room temperature for two hours, followed by evaporation in vacuo to dryness. The residue was treated with dilute aqueous 0.5N HCl (10 ml.), and then extracted with EtOAc (4×10 ml.). The combined extracts were dried (MgSO4) and evaporated. The residue was purified by preparative t.l.c. on silica gel plates using triethylamine/EtOH/EtOAc 1:1:9 v/v/v as developing solvent to give 2-chloro-6-[4-(3-[2-(2,2,2-trifluoroethyl)guanidino]pyrazol-1-yl)butoxy]pyrazine (170 mg.; 43%) having the following n.m.r. in d6DMSO: 8.25 (s, 2H); 7.4 (d, 1H); 5.6 (d, 1H); 4.25 (t, 2H); 3.9 (m, 4H); 1.7 (br m, 4H).

Workup

  1. customfollowed by evaporation in vacuo to dryness
  2. additionThe residue was treated with dilute aqueous 0.5N HCl (10 ml.)
  3. extractionextracted with EtOAc (4×10 ml.)
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by preparative t.l.c

Sources & evidence

ORD record
ord-c4d140be188a49419dded642b53cf71f
Source dataset
uspto-grants-1984_07
Patent number
US04463005

Reaction notes

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