Cesium carbonate → HCID 86665191, compound

HRID 2179451Notes

Reaction equation

HRID 2179451 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 Chiral Pak® AD® column (60% EtOH/hexanes with 0.1% diethylamine) to give the title compound (1st eluting enantiomer, 200 mg). MS 372.1 (M).

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-9b3796bdf7dc4ba283ae75b841c9d003
Source dataset
uspto-grants-2015_06
Patent number
US09067941B2

Reaction notes

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