Reaktion #162114

Reaktionsgleichung

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

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONA gelatinous mix
2. 2
   Sonstigeformed and after 4 min the mixture
3. 3
   Sonstigethe 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
   ExtraktionThe layer was extracted with EtOAc several times
8. 8
   Trocknendried over Na2SO4
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated in vacuo

Vorschrift

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).

Quelle