Réaction #162114

Équation de réaction

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

Solvants

acetonitrile

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONA gelatinous mix
2. 2
   Autreformed and after 4 min the mixture
3. 3
   Autrethe 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
   ExtractionThe layer was extracted with EtOAc several times
8. 8
   Séchagedried over Na2SO4
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated in vacuo

Mode opératoire

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).

Source