Hydrochloric Acid → N-(4-(3-Benzylpyrazin-2-yloxy)phenyl)pyridin-2-amine

HRID 473638Notes

Reaction equation

HRID 473638 reaction equation
Cl[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[Br-].[CH2:23]([Zn+])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1COCC1.Cl>>[CH2:23]([C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 53485989N-(4-(3-chloropyrazin-2-yloxy)phenyl)pyridin-2-amineHCID 178419772HCID 178419772, compound

Product 1

HCID 59374294N-(4-(3-Benzylpyrazin-2-yloxy)phenyl)pyridin-2-amine

Conditions

Temperature
70 °C

Procedure

A suspension of N-(4-(3-chloropyrazin-2-yloxy)phenyl)pyridin-2-amine (200 mg, 0.670 mmol), benzylzinc bromide, 0.5M in THF (6.7 mL, 3.35 mmol), and bis(di-t-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (80 mg, 0.11 mmol) was sparged with argon for 5 minutes then heated to 70° C. for 2 h. The reaction was then partitioned between EtOAc (30 mL) and sat NH4Cl (10 mL). The separated organic layer was dried over MgSO4, concentrated under reduced pressure, then purified on silica (40 g) eluting with 1.5-2.0% MeOH/DCM. The resulting residue was then dissolved in MeOH (5 mL) and 0.105 mL of HCl (5 M; 0.105 mL, 0.525 mmol) added. The resulting solid was isolated by filtration to give the title compound. MS (ESI positive ion) m/z: 355.1 (M+1). IC50 (uM) 0.250.

Workup

  1. customThe reaction was then partitioned between EtOAc (30 mL)
  2. dry with materialThe separated organic layer was dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. custompurified on silica (40 g)
  5. washeluting with 1.5-2.0% MeOH/DCM
  6. dissolutionThe resulting residue was then dissolved in MeOH (5 mL)
  7. customThe resulting solid was isolated by filtration

Sources & evidence

ORD record
ord-adeed2dc030f40139f78929909584496
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

Loading…