1,2-Dichloroethane → N-(6-(5-cyanopyrazin-2-ylamino)-4-(1-boc-piperidin-4-ylmethylamino)pyridin-3-yl)-2-(dimethylamino)acetamide

HRID 384632Notes

Reaction equation

HRID 384632 reaction equation
C(N(C(C)C)CC)(C)C.[CH3:10][N:11]([CH3:16])[CH2:12][C:13](O)=[O:14].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:31][C:32]1[C:33]([NH:47][CH2:48][CH:49]2[CH2:54][CH2:53][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:51][CH2:50]2)=[CH:34][C:35]([NH:38][C:39]2[CH:44]=[N:43][C:42]([C:45]#[N:46])=[CH:41][N:40]=2)=[N:36][CH:37]=1>CN(C=O)C>[C:45]([C:42]1[N:43]=[CH:44][C:39]([NH:38][C:35]2[N:36]=[CH:37][C:32]([NH:31][C:13](=[O:14])[CH2:12][N:11]([CH3:16])[CH3:10])=[C:33]([NH:47][CH2:48][CH:49]3[CH2:54][CH2:53][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:51][CH2:50]3)[CH:34]=2)=[N:40][CH:41]=1)#[N:46]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 673N,N-DimethylglycineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 59613544Tert-butyl 4-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate

Product 1

HCID 66746296N-(6-(5-cyanopyrazin-2-ylamino)-4-(1-boc-piperidin-4-ylmethylamino)pyridin-3-yl)-2-(dimethylamino)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diisopropylethylamine (16 μL, 0.092 mmol), N,N-dimethylglycine (7 mg, 0.067 mmol), HOBt (12 mg, 0.092 mmol) and EDC (17 mg, 0.092 mmol) were added to tert-butyl 4-((5-amino-2-(5-cyanopyrazin-2-ylamino)-pyridin-4-ylamino)-methyl)-piperidine-1-carboxylate (26 mg, 0.061 mmol) in DMF (1.5 mL). The mixture was stirred at room temperature for 6 hours and then partitioned between dichloromethane and water. The aqueous phase was extracted with dichloromethane. The combined organic layers were dried and concentrated. Preparative HPLC gave N-(6-(5-cyanopyrazin-2-ylamino)-4-(1-boc-piperidin-4-ylmethylamino)pyridin-3-yl)-2-(dimethylamino)acetamide as a white solid. The solid 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 and concentrated to give N-(6-(5-cyanopyrazin-2-ylamino)-4-(piperidin-4-ylmethylamino)pyridin-3-yl)-2-(dimethylamino)acetamide (7.52 mg, 30%) as a pale yellow solid.

Workup

  1. custompartitioned between dichloromethane and water
  2. extractionThe aqueous phase was extracted with dichloromethane
  3. customThe combined organic layers were dried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-4eb0e53ef97445b6bb44b6dd58282824
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

Loading…