Perfluorophenyl 2-cyanoacetate → HCID 178511186, compound

HRID 1854346Notes

Reaction equation

HRID 1854346 reaction equation
Cl.[C:2]1([C@@H:14]2[CH2:19][CH2:18][C@H:17]([NH2:20])[CH2:16][CH2:15]2)[N:6]2[C:7]3[CH:13]=[CH:12][NH:11][C:8]=3[N:9]=[CH:10][C:5]2=[N:4][N:3]=1.[C:21]([CH2:23][C:24](OC1C(F)=C(F)C(F)=C(F)C=1F)=[O:25])#[N:22]>C(Cl)Cl>[C:2]1([C@@H:14]2[CH2:15][CH2:16][C@H:17]([NH:20][C:24](=[O:25])[CH2:23][C:21]#[N:22])[CH2:18][CH2:19]2)[N:6]2[C:7]3[CH:13]=[CH:12][NH:11][C:8]=3[N:9]=[CH:10][C:5]2=[N:4][N:3]=1

Participants

4

Reactant 2

HCID 20402415Perfluorophenyl 2-cyanoacetateHCID 178479249HCID 178479249, compound

Product 1

HCID 178511186HCID 178511186, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of cis-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclohexanamine hydrochloride (0.106 g, 0.206 mmol, Example #D.1) in DCM (4 mL) was added TEA (0.086 mL, 0.62 mmol). The reaction mixture was sonicated until the reaction was homogeneous. To the reaction solution was added perfluorophenyl 2-cyanoacetate (0.078 g, 0.31 mmol, Preparation #6). The resulting solution was stirred at ambient temperature for about 16 h. The crude reaction mixture was purified by silica gel chromatography (40 g) eluting with a gradient of 0-20% EtOAc in DCM and then further purified by RP-HPLC (Table 2, Method e) to give N-(cis-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclohexyl)-2-cyanoacetamide with 3 equiv NH4OAc as an excipient (0.025 g, 22%). LC/MS (Table 2, Method a) Rt=1.33 min; MS m/z: 324 (M+H)+.

Workup

  1. customThe reaction mixture was sonicated until the reaction
  2. customThe crude reaction mixture
  3. customwas purified by silica gel chromatography (40 g)
  4. washeluting with a gradient of 0-20% EtOAc in DCM
  5. customfurther purified by RP-HPLC (Table 2, Method e)

Sources & evidence

ORD record
ord-812926be2dc145fdb2d8a5426f2d56b4
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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