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

HRID 1777998Notes

Reaction equation

HRID 1777998 reaction equation
CS(O[CH2:6][C:7]1[C:8]([CH:32]([O:35][CH3:36])[O:33][CH3:34])=[N:9][C:10]2[N:11]([C:17](=[O:31])[NH:18][C:19]3[CH:24]=[C:23]([O:25][CH:26]([CH3:28])[CH3:27])[C:22]([C:29]#[N:30])=[CH:21][N:20]=3)[CH2:12][CH2:13][CH2:14][C:15]=2[CH:16]=1)(=O)=O.[CH3:37][NH2:38]>C1COCC1.C([O-])(O)=O.[Na+].C(Cl)Cl>[C:29]([C:22]1[C:23]([O:25][CH:26]([CH3:27])[CH3:28])=[CH:24][C:19]([NH:18][C:17]([N:11]2[C:10]3[C:15](=[CH:16][C:7]([CH2:6][NH:38][CH3:37])=[C:8]([CH:32]([O:33][CH3:34])[O:35][CH3:36])[N:9]=3)[CH2:14][CH2:13][CH2:12]2)=[O:31])=[N:20][CH:21]=1)#[N:30]

Participants

6

Reactant 2

HCID 6329MethylamineHCID 118036581(8-((5-Cyano-4-isopropoxypyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl methanesulfonate2×

Product 1

HCID 118036812N-(5-cyano-4-isopropoxypyridin-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-isopropoxypyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl methanesulfonate (intermediate 167, 2.59 g, 4.98 mmol) in THF (83 ml) was added methylamine 2 M in THF (37.4 ml, 74.70 mmol) at ambient temperature and the reaction mixture was stirred at room temperature for approximately 4 h. The reaction mixture was diluted with saturated aqueous NaHCO3 and DCM. Phases were separated and the water phase was extracted with DCM (2×), organic phases were combined and dried using Na2SO4, filtered and concentrated to yield the title compound as a light yellow solid. (UPLC-MS 3) tR 0.88 min, ESI-MS 455.3 [M+H]+. 1H NMR (600 MHz, CDCl3) δ 14.00 (s, 1H), 8.37 (s, 1H), 7.95 (s, 1H), 7.61 (s, 1H), 5.51 (s, 1H), 4.88-4.79 (m, 1H), 4.06-4.01 (m, 2H), 3.86 (s, 2H), 3.50 (s, 6H), 2.88-2.80 (m, 2H), 2.49 (s, 3H), 2.03-1.96 (m, 2H), 1.43 (d, 6H).

Workup

  1. customPhases were separated
  2. extractionthe water phase was extracted with DCM (2×), organic phases
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-80a5531666ff48ba805c878e9353540a
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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