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

HRID 74932Notes

Reaction equation

HRID 74932 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][CH2:20][C@@H:19]4N)[C:14]([F:25])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.Cl[C:27]1C=C2C(C3N=C(N[C@H]4CCCC[C@@H]4N)C(F)=CN=3)=CN(S(C3C=CC(C)=CC=3)(=O)=O)C2=NC=1.C=O.[BH3-][C:64]#[N:65].[Na+]>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@H:18]4[CH2:23][CH2:22][CH2:21][CH2:20][C@@H:19]4[N:65]([CH3:64])[CH3:27])[C:14]([F:25])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 68007676(1S,2S)-N-[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[5,4-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]cyclohexane-1,2-diamineHCID 68008040(1S,2S)-N1-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-yl)cyclohexane-1,2-diamine

Product 1

HCID 68008162(1S,2S)-N1-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-yl)-N2,N2-dimethylcyclohexane-1,2-diamine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

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).

Workup

  1. additionA gelatinous mix
  2. customformed and after 4 min the mixture
  3. customthe reaction was quenched with 5 mL of 2N NaOH
  4. additionThe mixture was diluted with EtOAc
  5. stirringstirred until all solid
  6. dissolutiondissolved
  7. extractionThe layer was extracted with EtOAc several times
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-88d7f4518c1b401092ea6eb64812b685
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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