1,4-Dibromobutane → 5-(4-(Piperidin-3-ylmethylamino)-5-(pyrrolidin-1-yl)pyridin-2-ylamino)pyrazine-2-carbonitrile

HRID 384658Notes

Reaction equation

HRID 384658 reaction equation
[NH2:1][C:2]1[C:3]([NH:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]2)=[CH:4][C:5]([NH:8][C:9]2[CH:14]=[N:13][C:12]([C:15]#[N:16])=[CH:11][N:10]=2)=[N:6][CH:7]=1.[O-]CC.[Na+].Br[CH2:37][CH2:38][CH2:39][CH2:40]Br>C(O)C>[NH:21]1[CH2:22][CH2:23][CH2:24][CH:19]([CH2:18][NH:17][C:3]2[C:2]([N:1]3[CH2:40][CH2:39][CH2:38][CH2:37]3)=[CH:7][N:6]=[C:5]([NH:8][C:9]3[N:10]=[CH:11][C:12]([C:15]#[N:16])=[N:13][CH:14]=3)[CH:4]=2)[CH2:20]1

Participants

5

Reactant 3

HCID 80561,4-DibromobutaneHCID 2723922Sodium ethoxideHCID 66745373Tert-butyl 3-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate

Product 1

HCID 596135065-(4-(Piperidin-3-ylmethylamino)-5-(pyrrolidin-1-yl)pyridin-2-ylamino)pyrazine-2-carbonitrileYield 29%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

tert-Butyl 3-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate (40 mg, 0.094 mmol) (Synthesis 101-C) was dissolved in ethanol (2 mL) and treated with sodium ethoxide (34 mg, 0.509 mmol) and 1,4-dibromobutane (44 mg, 0.208 mmol) at between 70 and 80° C. for 96 h. The reaction was quenched with water and the aqueous phase extracted with dichloromethane. The combined organic phases were evaporated and the residue was treated with a 20% solution of TFA in dichloromethane for 20 min. The solution was evaporated and the residue was purified by HPLC to give 5-(4-(piperidin-3-ylmethylamino)-5-(pyrrolidin-1-yl)pyridin-2-ylamino)pyrazine-2-carbonitrile (10.3 mg, 29%).

Workup

  1. customThe reaction was quenched with water
  2. extractionthe aqueous phase extracted with dichloromethane
  3. customThe combined organic phases were evaporated
  4. additionthe residue was treated with a 20% solution of TFA in dichloromethane for 20 min
  5. customThe solution was evaporated
  6. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-b6dd81974be94469b37422252ed6e2da
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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