Phosphorus tribromide → 2-amino-4-((S)-1-(8-(5-hydroxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethylamino)pyrimidine-5-carbonitrile

HRID 1626915Notes

Reaction equation

HRID 1626915 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:12]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:13](=[O:29])[C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][C:15]=3[C:21]2[CH:22]=[N:23][CH:24]=[C:25]([O:27]C)[CH:26]=2)[CH3:10])[C:5]([C:36]#[N:37])=[CH:4][N:3]=1.P(Br)(Br)Br.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:12]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:13](=[O:29])[C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][C:15]=3[C:21]2[CH:22]=[N:23][CH:24]=[C:25]([OH:27])[CH:26]=2)[CH3:10])[C:5]([C:36]#[N:37])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 24614Phosphorus tribromideHCID 516892Sodium BicarbonateHCID 71270277(S)-2-amino-4-((1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile

Product 1

HCID 712704722-amino-4-((S)-1-(8-(5-hydroxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethylamino)pyrimidine-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of (S)-2-amino-4-((1-(8-(5-methoxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile 9 (15 mg, 0.031 mmol) in DCM (5 mL) at −78° C. under argon, PBr3 (77 mg, 0.31 mmol) was added and the resulting mixture was stirred from −78° C. to RT overnight. The reaction mixture was poured into ice-water (10 mL) and then neutralized with saturated aqueous NaHCO3 to adjust the pH value to 8-9. The mixture was extracted with a mixture of methanol in DCM (5%, 5×10 mL). The organic layer was dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel eluting with 1-3% MeOH/DCM to afford 2-amino-4-((S)-1-(8-(5-hydroxypyridin-3-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethylamino)pyrimidine-5-carbonitrile 13. ESI-MS m/z: 476.0 [M+H]+.

Workup

  1. extractionThe mixture was extracted with a mixture of methanol in DCM (5%, 5×10 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was purified by flash column chromatography on silica gel eluting with 1-3% MeOH/DCM

Sources & evidence

ORD record
ord-5f541615fbe44fef917abbc7f0e0edec
Source dataset
uspto-grants-2014_07
Patent number
US08785470B2

Reaction notes

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