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

HRID 1777997Notes

Reaction equation

HRID 1777997 reaction equation
CS(O[CH2:6][C:7]1[C:8]([CH:33]([O:36][CH3:37])[O:34][CH3:35])=[N:9][C:10]2[N:11]([C:17](=[O:32])[NH:18][C:19]3[CH:24]=[C:23]([NH:25][CH2:26][CH2:27][O:28][CH3:29])[C:22]([C:30]#[N:31])=[CH:21][N:20]=3)[CH2:12][CH2:13][CH2:14][C:15]=2[CH:16]=1)(=O)=O.[CH3:38][NH2:39]>C1COCC1.C([O-])(O)=O.[Na+].C(Cl)Cl>[C:30]([C:22]1[C:23]([NH:25][CH2:26][CH2:27][O:28][CH3:29])=[CH:24][C:19]([NH:18][C:17]([N:11]2[C:10]3[C:15](=[CH:16][C:7]([CH2:6][NH:39][CH3:38])=[C:8]([CH:33]([O:34][CH3:35])[O:36][CH3:37])[N:9]=3)[CH2:14][CH2:13][CH2:12]2)=[O:32])=[N:20][CH:21]=1)#[N:31]

Participants

6

Reactant 2

HCID 6329MethylamineHCID 118036268(8-((5-Cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl methanesulfonate2×

Product 1

HCID 118036536N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-((methylamino)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a suspension of (8-((5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl methanesulfonate (intermediate 170, 363 mg, 0.679 mmol) in THF (8 ml) was added methylamine 2 M in THF (5 ml, 10.00 mmol) at room temperature and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was diluted with saturated aqueous NaHCO3 and DCM. Phases were separated and the water phase was extracted with DCM (3×), organic phases were combined and dried using Na2SO4, filtered and concentrated. The crude product was purified using silica gel column chromatography eluting with a gradient of MeOH (including 3% NH3, 10-20%) in DCM. Fractions containing the product were combined and evaporated to yield the title compound as a colorless solid. (UPLC-MS 3) tR 0.70 min, ESI-MS 470.2 [M+H]+. 1H NMR (600 MHz, DMSO-d6) δ 13.60 (s, 1H), 8.27 (s, 1H), 7.74 (s, 1H), 7.53 (s, 1H), 6.92 (t, 1H), 5.50 (s, 1H), 3.96-3.91 (m, 2H), 3.73 (s, 2H), 3.53 (t, J=5.8 Hz, 2H), 3.42-3.34 (m, 8H), 3.30 (s, 3H), 2.84 (t, 2H), 2.28 (s, 3H), 1.95-1.87 (m, 2H).

Workup

  1. customPhases were 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 a gradient of MeOH (including 3% NH3, 10-20%) in DCM
  8. additionFractions containing the product
  9. customevaporated

Sources & evidence

ORD record
ord-8909c57773494464a52a90bbefbc540a
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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