反応 #43419

反応方程式

sodium bicarbonate

chloroform methanol

(4S)-4-[(4-amino-1-piperidinyl)methyl]-3,8-difluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

[1,3]oxathiolo[5,4-c]pyridine-6-carbaldehyde

sodium triacetoxyborohydride

→

title compound

収率 36.0%

(4S)-3,8-Difluoro-4-hydroxy-4-({4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one dihydrochloride

収率 36.0%

反応条件

後処理

1. 1
   抽出The aqueous layer was extracted with a 10% solution of methanol in dichloromethane (3×200 ml)
2. 2
   乾燥The combined organic extracts were dried over magnesium sulphate
3. 3
   その他evaporated
4. 4
   その他The residue was chromatographed
5. 5
   洗浄eluting with a 0-20% gradient of methanol in dichloromethane
6. 6
   その他to yield 82 mg initially

実験手順

A solution of (4S)-4-[(4-amino-1-piperidinyl)methyl]-3,8-difluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one (E1 enantiomer) (180 mg, 0.536 mmol) and [1,3]oxathiolo[5,4-c]pyridine-6-carbaldehyde (89 mg, 0.536 mmol) (for a synthesis, see WO2004058144, Example 61) in chloroform/methanol (5 ml/0.5 ml) was stirred at room temperature under argon for 1 h before treatment with sodium triacetoxyborohydride (341 mg, 1.608 mmol). After 1 h stirring the reaction mixture was treated with saturated sodium bicarbonate (20 ml). The aqueous layer was extracted with a 10% solution of methanol in dichloromethane (3×200 ml). The combined organic extracts were dried over magnesium sulphate and evaporated. The residue was chromatographed eluting with a 0-20% gradient of methanol in dichloromethane to yield 82 mg initially and 13 mg by re-chromatographing mixed fractions of the free base of the title compound as a yellow solid (95 mg, 36%).

出典