Piperazine → 2-Chloro-4-(4-(methylsulfonyl)piperazin-1-yl)furo[3,2-d]pyrimidine

HRID 1038807Notes

Reaction equation

HRID 1038807 reaction equation
Cl.[Cl:2][C:3]1[N:4]=[C:5]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[C:6]2[O:11][CH:10]=[CH:9][C:7]=2[N:8]=1.ClC1N=C(Cl)C2OC=CC=2N=1.N1CCNCC1.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>N1C=CC=CC=1.C(Cl)Cl>[Cl:2][C:3]1[N:4]=[C:5]([N:12]2[CH2:17][CH2:16][N:15]([S:36]([CH3:35])(=[O:38])=[O:37])[CH2:14][CH2:13]2)[C:6]2[O:11][CH:10]=[CH:9][C:7]=2[N:8]=1

Participants

7

Reactant 4

HCID 4837PiperazineHCID 31297Methanesulfonyl chlorideHCID 457899682,4-Dichlorofuro[3,2-D]pyrimidineHCID 1317308902-Chloro-4-(piperazin-1-yl)furo[3,2-d]pyrimidine, hydrochloride salt

Product 1

HCID 866650952-Chloro-4-(4-(methylsulfonyl)piperazin-1-yl)furo[3,2-d]pyrimidineYield 43%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a flask was added 2-chloro-4-(piperazin-1-yl)furo[3,2-d]pyrimidine, hydrochloride salt (0.325 g, 1.18 mmol, prepared using A from 2,4-dichlorofuro[3,2-d]pyrimidine [Ark Pharm] with piperazine), DCM (7 mL), pyridine (7.00 mL) and MsCl (0.101 mL, 1.29 mmol). The mixture was stirred overnight at rt. The mixture was warmed to about 35° C. and stirred for about 5 h. The solvent was removed in vacuo and the residue dissolved in DCM (20 mL). The organics were washed with water (about 20 mL) and with saturated aqueous NaHCO3 (about 20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography with an elution gradient EtOAc/hexanes (50 to 75%) to give 2-chloro-4-(4-(methylsulfonyl)piperazin-1-yl)furo[3,2-d]pyrimidine (0.162 g, 43%): LC/MS (Table 2, Method a) Rt=1.11 min; MS m/z 317.2 (M+H)+.

Workup

  1. customprepared
  2. temperatureThe mixture was warmed to about 35° C.
  3. stirringstirred for about 5 h
  4. customThe solvent was removed in vacuo
  5. dissolutionthe residue dissolved in DCM (20 mL)
  6. washThe organics were washed with water (about 20 mL) and with saturated aqueous NaHCO3 (about 20 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography with an elution gradient EtOAc/hexanes (50 to 75%)

Sources & evidence

ORD record
ord-c13038ed5de94278aecb5345b6dc0ba5
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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