Acetic Acid → (R)-5-(1-amino-3-cyclopropyl-1-oxopropan-2-ylamino)-3-(thieno[2,3-b]pyridin-3-ylamino)pyrazine-2-carboxamide

HRID 332737Notes

Reaction equation

HRID 332737 reaction equation
[C:1]([C:3]1[N:4]=[CH:5][C:6]([NH:19][C@H:20]([CH2:24][CH:25]2[CH2:27][CH2:26]2)[C:21]([NH2:23])=[O:22])=[N:7][C:8]=1[NH:9][C:10]1[C:18]2[C:13](=[N:14][CH:15]=[CH:16][CH:17]=2)[S:12][CH:11]=1)#[N:2].[OH-].[Na+].OO.CC(O)=[O:34]>CCO.CS(C)=O>[NH2:23][C:21](=[O:22])[C@H:20]([NH:19][C:6]1[N:7]=[C:8]([NH:9][C:10]2[C:18]3[C:13](=[N:14][CH:15]=[CH:16][CH:17]=3)[S:12][CH:11]=2)[C:3]([C:1]([NH2:2])=[O:34])=[N:4][CH:5]=1)[CH2:24][CH:25]1[CH2:26][CH2:27]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 86685543(R)-2-(5-cyano-6-(thieno[2,3-b]pyridin-3-ylamino)pyrazin-2-ylamino)-3-cyclopropylpropanamide

Product 1

HCID 71573436(R)-5-(1-amino-3-cyclopropyl-1-oxopropan-2-ylamino)-3-(thieno[2,3-b]pyridin-3-ylamino)pyrazine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolvent

Procedure

A mixture of (R)-2-(6-chloro-5-cyanopyrazin-2-ylamino)-3-cyclopropylpropanamide (78 mg, 0.293 mmol), thieno[2,3-b]pyridin-3-amine (60 mg, 0.400 mmol), K2CO3 (70 mg, 0.507 mmol), BINAP (25 mg, 0.040 mmol) and Pd(OAc)2 (10 mg, 0.044 mmol) in dioxane (2 mL) was degassed with Ar, then was stirred at 110 C for 3 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give (R)-2-(5-cyano-6-(thieno[2,3-b]pyridin-3-ylamino)pyrazin-2-ylamino)-3-cyclopropylpropanamide (33 mg). The compound (R)-2-(5-cyano-6-(thieno[2,3-b]pyridin-3-ylamino)pyrazin-2-ylamino)-3-cyclopropylpropanamide (33 mg, 0.087 mmol) was dissolved in EtOH (2 mL) and DMSO (1 mL), aq. 1N NaOH (1.0 mL) and aq. H2O2 (30%, 1.0 mL) were added. The mixture was stirred at room temperature for 30 min. HOAc (0.5 mL) was added. The mixture was then concentrated in vacuo. The residue was purified by HPLC to give the titled compound (34 mg). MS 398.2 (M+H); UV 203.6, 224.8, 262.1, 294.1, 357.3 nm; t 0.532 min.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-f6f82b50805e46c8934f9757321425ad
Source dataset
uspto-grants-2014_11
Patent number
US08877760B2

Reaction notes

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