Cesium carbonate → HCID 86665191, compound

HRID 448208Notes

Reaction equation

HRID 448208 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[N:7][C:8]=1[CH2:9]Cl.[Cl:18][C:19]1[C:20]2[CH2:27][C:26](=[O:28])[NH:25][C:21]=2[N:22]=[CH:23][N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[Br-].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:18][C:19]1[C:20]2[C@:27]3([CH2:9][C:8]4=[N:7][CH:6]=[C:5]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:4]=[C:3]4[CH2:2]3)[C:26](=[O:28])[NH:25][C:21]=2[N:22]=[CH:23][N:24]=1

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 253881Sodium BromideHCID 516892Sodium BicarbonateHCID 120958704-chloro-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-6-oneHCID 68749545HCID 68749545, compound

Product 1

HCID 86665191HCID 86665191, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 5,6-bis(chloromethyl)pyridine-3-carboxylate (1.80 g, 6.52 mmol) in N,N-dimethylformamide (93.0 mL) was added 4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1.80 g, 10.62 mmol), cesium carbonate (3.65 g, 11.21 mmol), and sodium bromide (0.671 g, 6.52 mmol). After 30 min, saturated aqueous sodium bicarbonate was added and the mixture was washed with ethyl acetate (3×). The combined organics were washed with water (3×), brine (3×) and were dried with magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→10% methanol/dichloromethane) then a second purification by silica gel chromatography (100% dichloromethane→30% ethyl acetate/dichloromethane) gave the title compound as a racemic mixture. Chiral separation of the individual enantiomers was accomplished by use of HPLC using a 10 cm ChiralPak® AD column (60% EtOH/hexanes with 0.1% diethylamine) to give the title compound as the 1st eluting enantiomer. MS: m/z=373.2 (M+1).

Workup

  1. washthe mixture was washed with ethyl acetate (3×)
  2. washThe combined organics were washed with water (3×), brine (3×)
  3. dry with materialwere dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (100% dichloromethane→10% methanol/dichloromethane)
  7. customa second purification by silica gel chromatography (100% dichloromethane→30% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-e9c11f4782934ea4a4314d49662c20c8
Source dataset
uspto-grants-2013_07
Patent number
US08481556B2

Reaction notes

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