Cesium carbonate → HCID 86665191, compound

HRID 588985Notes

Reaction equation

HRID 588985 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-696b81b3b8254bcf81c2fe91915f8a28
Source dataset
uspto-grants-2016_01
Patent number
US09227973B2

Reaction notes

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