반응 #493712

반응 방정식

tert-butyl 5,6-bis(chloromethyl)pyridine-3-carboxylate

4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

cesium carbonate

sodium bromide

sodium bicarbonate

→

title compound

tert-Butyl (6S)-4′-chloro-6′-oxo-5,6′,7,7′-tetrahydrospiro[cyclopenta[b]pyridine-6,5′-pyrrolo[2,3-d]pyrimidine]-3-carboxylate

용매

N,N-dimethylformamide

반응 조건

후처리

1. 1
   세척the mixture was washed with ethyl acetate (3×)
2. 2
   세척The combined organics were washed with water (3×), brine (3×)
3. 3
   건조were dried with magnesium sulfate
4. 4
   여과filtered
5. 5
   농축concentrated
6. 6
   기타Purification by silica gel chromatography (100% dichloromethane→10% methanol/dichloromethane)
7. 7
   기타a second purification by silica gel chromatography (100% dichloromethane→30% ethyl acetate/dichloromethane)

실험 절차

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).

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