Water → 7-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-8-pyrrolidin-1-yl-3,7-dihydro-1H-purine-2,6-dione

HRID 1727034Notes

Reaction equation

HRID 1727034 reaction equation
Br[C:2]1[N:10]([CH2:11][C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:19])[C:9]2[C:8](=[O:20])[N:7]([CH3:21])[C:6](=[O:22])[N:5]([CH3:23])[C:4]=2[N:3]=1.[NH:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1.O>CS(C)=O>[Cl:19][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([F:18])[C:12]=1[CH2:11][N:10]1[C:9]2[C:8](=[O:20])[N:7]([CH3:21])[C:6](=[O:22])[N:5]([CH3:23])[C:4]=2[N:3]=[C:2]1[N:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 962WaterHCID 31268PyrrolidineHCID 6592358-bromo-7-(2-chloro-6-fluorobenzyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione

Product 1

HCID 37435577-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-8-pyrrolidin-1-yl-3,7-dihydro-1H-purine-2,6-dioneYield 102.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

A solution of 8-bromo-7-(2-chloro-6-fluorobenzyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (50 mg, 0.12 mmol) in 300 μL DMSO was treated with pyrrolidine (55 μL, 0.55 mmol) and heated at 130° C. for 15 h. The reaction was cooled to 25° C. and treated with 1 mL H2O. After centrifugation for 1 h the liquid was decanted, and the process was repeated. The reaction was treated with 1 mL toluene and concentrated under reduced pressure. The residue was treated with 2 mL CH2Cl2 followed by isocyanate scavenger resin (500 mg, 0.58 mmol, 1.16 mmol/g). The reaction was filtered after agitating for 30 min, and the filtrate was concentrated under reduced pressure to give 48 mg (>99% yield) of the title compound: 1H NMR (CDCl3, 300 MHz) 7.27-7.18 (m, 2H), 7.02-6.91 (m, 1H), 5.73 (s, 2H), 3.59-3.48 (m, 7H), 3.35 (s, 3H), 1.98-1.87 (m, 4H); MS (ESP+) m/e 392 (MH+); TLC (EtOAc:hexanes/1:1) Rf=0.24.

Workup

  1. temperatureThe reaction was cooled to 25° C.
  2. customAfter centrifugation for 1 h the liquid was decanted
  3. additionThe reaction was treated with 1 mL toluene
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was treated with 2 mL CH2Cl2
  6. filtrationThe reaction was filtered
  7. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-91a01897503844e88a5dbdd867b82ab3
Source dataset
uspto-grants-2009_02
Patent number
US07495004B2

Reaction notes

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