反応 #162114

反応方程式

NaCNBH3

(1S,2S)—N1-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-yl)cyclohexane-1,2-diamine

23b

(1S,2S)—N1-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-yl)cyclohexane-1,2-diamine

formaldehyde

→

desired product

(1S,2S)—N1-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-yl)-N2,N2-dimethylcyclohexane-1,2-diamine

溶媒

acetonitrile

反応条件

後処理

1. 1
   workup.ADDITIONA gelatinous mix
2. 2
   その他formed and after 4 min the mixture
3. 3
   その他the reaction was quenched with 5 mL of 2N NaOH
4. 4
   workup.ADDITIONThe mixture was diluted with EtOAc
5. 5
   workup.STIRRINGstirred until all solid
6. 6
   workup.DISSOLUTIONdissolved
7. 7
   抽出The layer was extracted with EtOAc several times
8. 8
   乾燥dried over Na2SO4
9. 9
   ろ過filtered
10. 10
    濃縮concentrated in vacuo

実験手順

To a mixture of (1S,2S)—N1-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-yl)cyclohexane-1,2-diamine, 23b, (0.08 g, 0.22 mmol) in acetonitrile (1.6 mL) at room temperature was added formaldehyde (0.09 mL of 37% w/v, 1.11 mmol) followed by NaCNBH3 (0.04 g, 0.56 mmol). A gelatinous mix formed and after 4 min the mixture became fluid again. After 4 hours, the reaction was quenched with 5 mL of 2N NaOH and the mixture was stirred overnight. The mixture was diluted with EtOAc and stirred until all solid dissolved. The layer was extracted with EtOAc several times, dried over Na2SO4, filtered and concentrated in vacuo. Silica gel chromatography (0-15% MeOH—CH2Cl2) followed by preparatory HPLC provided the desired product, which was converted to the corresponding HCl salt with HCl (4N in dioxane).

出典