Methylamine → (racemic) N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(1-(methylamino)ethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777992Notes

Reaction equation

HRID 1777992 reaction equation
CS(O[CH:6]([C:8]1[C:9]([CH:34]([O:37][CH3:38])[O:35][CH3:36])=[N:10][C:11]2[N:12]([C:18](=[O:33])[NH:19][C:20]3[CH:25]=[C:24]([NH:26][CH2:27][CH2:28][O:29][CH3:30])[C:23]([C:31]#[N:32])=[CH:22][N:21]=3)[CH2:13][CH2:14][CH2:15][C:16]=2[CH:17]=1)[CH3:7])(=O)=O.[CH3:39][NH2:40]>C(Cl)Cl.CN(C=O)C.O>[C:31]([C:23]1[C:24]([NH:26][CH2:27][CH2:28][O:29][CH3:30])=[CH:25][C:20]([NH:19][C:18]([N:12]2[C:11]3[C:16](=[CH:17][C:8]([CH:6]([NH:40][CH3:39])[CH3:7])=[C:9]([CH:34]([O:37][CH3:38])[O:35][CH3:36])[N:10]=3)[CH2:15][CH2:14][CH2:13]2)=[O:33])=[N:21][CH:22]=1)#[N:32]

Participants

6

Reactant 2

HCID 6329MethylamineHCID 118036849(Racemic) 1-(8-((5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)ethyl methanesulfonate2×

Product 1

HCID 118036356(racemic) N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(1-(methylamino)ethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of (racemic) 1-(8-((5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)ethyl methanesulfonate (intermediate 182, 231 mg, 0.421 mmol) in DCM (8 ml) and DMF (0.5 ml) at 0° C. was added methylamine (2M in THF, 3 mL, 6.00 mmol). The reaction mixture was allowed to warm to room temperature and continued to stir over night. The reaction mixture was diluted with water and DCM, phases were separated and the water phase was extracted with DCM (3×), organic phases were combined, dried using Na2SO4, filtered and concentrated. The crude product was purified using silica gel column chromatography eluting with MeOH (including 3% NH3, 4-5%) in DCM to yield the title compound as a colorless solid. (UPLC-MS 3) tR 0.76 min, ESI-MS 484.2 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 13.70 (s, 1H), 8.18 (s, 1H), 8.09 (s, 1H), 7.55 (s, 1H), 5.42 (s, 1H), 5.25 (t, 1H), 4.80-4.70 (m, 1H), 4.11-3.93 (m, 2H), 3.62 (t, 2H), 3.52-3.42 (m, 8H), 3.39 (s, 3H), 2.99-2.81 (m, 2H), 2.38 (s, 3H), 2.05-1.93 (m, 2H), 1.54 (d, J=6.6 Hz, 3H), 1.24 (s, 1H).

Workup

  1. customwere separated
  2. extractionthe water phase was extracted with DCM (3×), organic phases
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified
  7. washeluting with MeOH (including 3% NH3, 4-5%) in DCM

Sources & evidence

ORD record
ord-16dd6213d75b46b281cb5f4cac3b1daf
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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