Triethylamine → N-(6-(5-cyanopyrazin-2-ylamino)-4-(1-Boc-piperidin-4-ylmethylamino)pyridin-3-yl)ethanesulfonamide

HRID 556794Notes

Reaction equation

HRID 556794 reaction equation
C(N(CC)CC)C.[CH2:8]([S:10](Cl)(=[O:12])=[O:11])[CH3:9].[NH2:14][C:15]1[C:16]([NH:30][CH2:31][CH:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]2)=[CH:17][C:18]([NH:21][C:22]2[CH:27]=[N:26][C:25]([C:28]#[N:29])=[CH:24][N:23]=2)=[N:19][CH:20]=1>CN(C=O)C>[C:28]([C:25]1[N:26]=[CH:27][C:22]([NH:21][C:18]2[N:19]=[CH:20][C:15]([NH:14][S:10]([CH2:8][CH3:9])(=[O:12])=[O:11])=[C:16]([NH:30][CH2:31][CH:32]3[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]3)[CH:17]=2)=[N:23][CH:24]=1)#[N:29]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 11667Ethanesulfonyl chloride2×HCID 59613544Tert-butyl 4-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate

Product 1

HCID 66745434N-(6-(5-cyanopyrazin-2-ylamino)-4-(1-Boc-piperidin-4-ylmethylamino)pyridin-3-yl)ethanesulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Triethylamine (15 μL, 0.11 mmol) and ethylsulfonylchloride (8 μL, 0.78 mmol) were added to a stirred solution of tert-butyl 4-((5-amino-2-(5-cyanopyrazin-2-ylamino)-pyridin-4-ylamino)-methyl)-piperidine-1-carboxylate (30.3 mg, 0.071 mmol) in DMF (1 mL) at 0° C. After 1.5 hours at room temperature, further ethylsulfonylchloride (5.5 μL, 0.53 mmol) and triethylamine (7.5 μL, 0.53 mmol) were added. After 1 hour the reaction mixture was partitioned between dichloromethane and water. The aqueous phase was extracted with dichloromethane. The combined organic phases were dried (Na2SO4) and concentrated. Preparative HPLC gave N-(6-(5-cyanopyrazin-2-ylamino)-4-(1-Boc-piperidin-4-ylmethylamino)pyridin-3-yl)ethanesulfonamide as a solid. The material was dissolved in 20% trifluoroacetic acid in dichloromethane. After 20 minutes the mixture was loaded onto a MP-TsOH SPE cartridge and eluted with 2M ammonia in methanol. The basic fractions were combined to give N-(6-(5-cyanopyrazin-2-ylamino)-4-(piperidin-4-ylmethylamino)pyridin-3-yl)ethanesulfonamide (2.28 mg, 8%).

Workup

  1. customAfter 1 hour the reaction mixture was partitioned between dichloromethane and water
  2. extractionThe aqueous phase was extracted with dichloromethane
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-e3efb077d8974ddfa338fbaf91e9cb68
Source dataset
uspto-grants-2011_11
Patent number
US08058045B2

Reaction notes

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