1,1'-Carbonyldiimidazole → HCID 89934139, compound

HRID 921959Notes

Reaction equation

HRID 921959 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][C@@H:11]([NH:14][CH:15]3[CH2:18][O:17][CH2:16]3)[C@H:10]([OH:19])[CH2:9]2)=[CH:6][C:5]([C:20]#[N:21])=[CH:4][C:3]=1[NH:22][C:23]1[N:28]=[C:27]([NH:29][CH2:30][CH3:31])[C:26]2=[N:32][CH:33]=[C:34]([C:35]#[N:36])[N:25]2[N:24]=1.[C:37](N1C=CN=C1)(N1C=CN=C1)=[O:38]>CN(C=O)C>[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][C@H:11]3[N:14]([CH:15]4[CH2:16][O:17][CH2:18]4)[C:37](=[O:38])[O:19][C@@H:10]3[CH2:9]2)=[CH:6][C:5]([C:20]#[N:21])=[CH:4][C:3]=1[NH:22][C:23]1[N:28]=[C:27]([NH:29][CH2:30][CH3:31])[C:26]2=[N:32][CH:33]=[C:34]([C:35]#[N:36])[N:25]2[N:24]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 89922391HCID 89922391, compound

Product 1

HCID 89934139HCID 89934139, compoundYield 51.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To (+/−)-2-((2-chloro-5-cyano-3-((3R,4R)-3-hydroxy-4-(oxetan-3-ylamino)piperidin-1-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (90 mg, 0.177 mmol) in DMF (5 mL) was added 1,1′-carbonyldiimidazole (200 mg, 1.233 mmol) and the reaction stirred at 25° C. 16 hr. The crude material was purified via preparative LC/MS with the following conditions: Column: XBridge C18, 19×mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile: water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 10-mM ammonium acetate; Gradient: 30-70% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford rac-2-((2-chloro-5-cyano-3-((3aR,7aR)-1-(oxetan-3-yl)-2-oxohexahydrooxazolo[5,4-c]pyridin-5 (2H)-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (48.8 mg).

Workup

  1. custom16 hr
  2. customThe crude material was purified via preparative LC/MS with the following conditions
  3. customa 5-minute hold
  4. additionFractions containing the desired product
  5. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-522d4bdaf07c406ea0cb53cb435f0fa5
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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