Imidazole → HCID 178465187, compound

HRID 1420318Notes

Reaction equation

HRID 1420318 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([C:18]([NH:20][CH2:21][CH3:22])=[O:19])[C@@H:14]([OH:15])[C@H:12]2[OH:13])=[C:4]([NH:23][CH2:24][CH:25]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:3]=1.[CH2:38]([NH2:41])[CH2:39][NH2:40].Cl.[N:43]1(C(N)=N)[CH:47]=CC=[N:44]1.N1C=CN=C1>CS(C)=O.CO>[NH2:44][N:43]=[CH:47][NH:40][CH2:39][CH2:38][NH:41][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([C:18]([NH:20][CH2:21][CH3:22])=[O:19])[C@@H:14]([OH:15])[C@H:12]2[OH:13])=[C:4]([NH:23][CH2:24][CH:25]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:3]=1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 3301EthylenediamineHCID 2734672Pyrazole-1-carboxamidine monohydrochloride2×HCID 86647542HCID 86647542, compound

Product 1

HCID 178465187HCID 178465187, compoundYield 57.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

A solution of 1-[2-chloro-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl]-1-deoxy-N-ethyl-β-D-ribofuranuronamide (0.382 g, 0.73 mmol) in dimethylsulphoxide (2.5 ml) was heated at 125° for 18 h with ethylenediamine (1.15 g, 19.2 mmol) under nitrogen. The cooled mixture was partitioned between ethyl acetate (50 ml) and water (50 ml) and the aqueous phase was separated, extracted with ethyl acetate (20 ml) and the extract was combined with the organic phase from the partitioning. The organic solution was dried (MgSO4) and evaporated to leave a brown froth (0.373 g). This froth (0.353 g) was dissolved in 50% aqueous methanol (20 ml) and the solution was heated at 50° with pyrazole-1-carboxamidine hydrochloride (0.099 g, 0.675 mmol) for 18 h. More pyrazole-1-carboxamidine hydrochloride (0.099 g, 0.675 mmol) and imidazole (0.048 g, 0.705 mmol) were added and the reaction was heated at 50° for a further 18 h. The mixture was evaporated to leave a red oil which was purified by preparative HPLC (20-60% acetonitrile) to give the title compound (0.23 g) as a solid from ether. The product had MH+ =589, nmr(δ,DMSO-d6) includes 1.02(t,3H), 3.05-3.25(m,2H) 3.3-3.5(m,2H), 3.4-3.6(m,1H), 4.8(s,1H), 4.5-4.7(m,2H), 5.85(d,1H), 7.15-7.4(m,10H), 7.57(m,1H), 8.12(s,1H), 8.1-8.25(m,1H).

Workup

  1. customThe cooled mixture was partitioned between ethyl acetate (50 ml) and water (50 ml)
  2. customthe aqueous phase was separated
  3. extractionextracted with ethyl acetate (20 ml)
  4. dry with materialThe organic solution was dried (MgSO4)
  5. customevaporated
  6. customto leave a brown froth (0.373 g)
  7. temperaturethe reaction was heated at 50° for a further 18 h
  8. customThe mixture was evaporated
  9. customto leave a red oil which
  10. customwas purified by preparative HPLC (20-60% acetonitrile)

Sources & evidence

ORD record
ord-8296ceb624594ae6ab697e94acb6220e
Source dataset
uspto-grants-1999_03
Patent number
US05889178

Reaction notes

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