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

HRID 1777994Notes

Reaction equation

HRID 1777994 reaction equation
F.N1C=CC=CC=1.[Si]([O:15][CH:16]([C:18]1[CH:19]=[C:20]2[C:25](=[N:26][C:27]=1[CH:28]([O:31][CH3:32])[O:29][CH3:30])[N:24]([C:33]([NH:35][C:36]1[CH:41]=[C:40]([NH:42][CH2:43][CH2:44][O:45][CH3:46])[C:39]([C:47]#[N:48])=[CH:38][N:37]=1)=[O:34])[CH2:23][CH2:22][CH2:21]2)[CH3:17])(C(C)(C)C)(C)C.C([O-])(O)=O.[Na+].C(Cl)Cl>C1COCC1>[C:47]([C:39]1[C:40]([NH:42][CH2:43][CH2:44][O:45][CH3:46])=[CH:41][C:36]([NH:35][C:33]([N:24]2[C:25]3[C:20](=[CH:19][C:18]([CH:16]([OH:15])[CH3:17])=[C:27]([CH:28]([O:31][CH3:32])[O:29][CH3:30])[N:26]=3)[CH2:21][CH2:22][CH2:23]2)=[O:34])=[N:37][CH:38]=1)#[N:48]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 64774Pyridine, hydrofluoride (1:1)HCID 516892Sodium BicarbonateHCID 131734796(racemic) 6-(1-((tert-butyldimethylsilyl)oxy)ethyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2×

Product 1

HCID 118036612(racemic) N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(1-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Pyridine hydrofluoride (0.130 ml, 1.012 mmol) was added to a suspension of (racemic) 6-(1-((tert-butyldimethylsilyl)oxy)ethyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 184, 296 mg, 0.506 mmol) in THF (2.5 ml) and stirred for 18 h. The reaction mixture was poured into saturated aqueous NaHCO3 and DCM was added. Phases were separated and the water phase was back 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 (0-4%) in DCM to yield the title compound as a colorless solid. (UPLC-MS 3) tR 0.90 min, ESI-MS 471.2 [M+H]+. 1H NMR (600 MHz, DMSO-d6) δ 13.62 (s, 1H), 8.27 (s, 1H), 7.84 (s, 1H), 7.53 (s, 1H), 6.92 (t, 1H), 5.45 (s, 1H), 5.23-5.16 (m, 2H), 3.98-3.88 (m, 2H), 3.53 (t, 2H), 3.41-3.31 (m, 8H), 3.30 (s, 3H), 2.89-2.83 (m, 2H), 1.95-1.86 (m, 2H), 1.30 (d, 3H).

Workup

  1. additionwas added
  2. customPhases were separated
  3. extractionthe water phase was back extracted with DCM (3×)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified
  8. washeluting with MeOH (0-4%) in DCM

Sources & evidence

ORD record
ord-482fb60b4f85448194254ae78ed9b3b5
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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