1,2-Dichloroethane → (+/-)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamide

HRID 921730Notes

Reaction equation

HRID 921730 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:17][CH2:16][C@@H:15]3[C@H:10]([O:11][CH2:12][C:13](=[O:18])[NH:14]3)[CH2:9]2)=[CH:6][C:5]([C:19]#[N:20])=[CH:4][C:3]=1[NH:21]C1N=C(N(CC)CC2C=CC(OC)=CC=2)C2=NC=C(C#N)N2N=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O.[Cl:60]CCCl>>[NH2:21][C:3]1[C:2]([Cl:1])=[C:7]([N:8]2[CH2:17][CH2:16][C@@H:15]([NH:14][C:13](=[O:18])[CH2:12][Cl:60])[C@H:10]([OH:11])[CH2:9]2)[CH:6]=[C:5]([C:19]#[N:20])[CH:4]=1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 86708612(+/-)-2-((2-chloro-5-cyano-3-((4aR,8aR)-2-oxohexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)phenyl)amino)-4-(ethyl (4 methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 86708610(+/-)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamide

Conditions

Temperature
25 °C

Procedure

(+/−)-2-((2-chloro-5-cyano-3-((4aR,8aR)-2-oxohexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)phenyl)amino)-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile was taken up in DCE (0.8 mL), anisole (0.043 mL, 0.391 mmol) and TFA (0.5 mL, 6.49 mmol). The mixture stirred 2 h at 25° C. and solvent was removed. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×200 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 20-mM ammonium acetate; Gradient: 25-65% 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 (+/−)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamide (2.2 mg).

Workup

  1. customsolvent was removed
  2. customThe crude material was purified via preparative LC/MS with the following conditions
  3. waitGradient: 25-65% B over 20 minutes
  4. customa 5-minute hold
  5. additionFractions containing the desired product
  6. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-d34dd794d37e49b38f444caeadac2dea
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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