2-Amino-5-cyanopyridine → 6-bromo-N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1778042Notes

Reaction equation

HRID 1778042 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH:12]([O:15][CH3:16])[O:13][CH3:14])[N:8]([C:17]([O:19]C1C=CC=CC=1)=O)[CH2:7][CH2:6][CH2:5]2.[NH2:26][C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][N:28]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[N:10][C:11]=1[CH:12]([O:13][CH3:14])[O:15][CH3:16])[N:8]([C:17]([NH:26][C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][N:28]=1)=[O:19])[CH2:7][CH2:6][CH2:5]2

Participants

5

Reactant 3

HCID 8182602-Amino-5-cyanopyridineHCID 2733832Lithium HexamethyldisilazideHCID 118036767phenyl 6-bromo-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate2×

Product 1

HCID 1180363436-bromo-N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of phenyl 6-bromo-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 11, 640 mg, 1.57 mmol) and 6-aminonicotinonitrile (206 mg, 1.73 mmol) in THF (10 ml) at −10° C. was treated with LHMDS (1M in THF, 1.89 ml, 1.89 mmol) and stirred for 2 h. The reaction mixture was quenched with saturated aqueous NH4Cl. The org. layer was washed with water (2×) and brine, dried over Na2SO4, filtered and concentrated under vacuum. The crude material was dissolved in a small quantity of DCM and then, MeOH was added to precipitate the product. The white solid was collected by filtration and washed with MeOH to obtain the title compound as a white solid. (UPLC-MS 1) tR 1.18 min; ESI-MS 432.0, 434.0 [M+H]+.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous NH4Cl
  2. washlayer was washed with water (2×) and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. dissolutionThe crude material was dissolved in a small quantity of DCM
  7. additionMeOH was added
  8. customto precipitate the product
  9. filtrationThe white solid was collected by filtration
  10. washwashed with MeOH

Sources & evidence

ORD record
ord-7a48fc0a1b5f4baaafae87da646fa873
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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