Hydrochloric Acid → N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-(hydroxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1778090Notes

Reaction equation

HRID 1778090 reaction equation
[Si]([O:8][CH2:9][C:10]1[CH:11]=[C:12]2[C:17](=[N:18][C:19]=1[CH:20](OC)[O:21]C)[N:16]([C:25]([NH:27][C:28]1[CH:33]=[C:32]([NH:34][CH2:35][CH2:36][O:37][CH3:38])[C:31]([C:39]#[N:40])=[CH:30][N:29]=1)=[O:26])[CH2:15][CH2:14][CH2:13]2)(C(C)(C)C)(C)C.O.Cl>C1COCC1>[C:39]([C:31]1[C:32]([NH:34][CH2:35][CH2:36][O:37][CH3:38])=[CH:33][C:28]([NH:27][C:25]([N:16]2[C:17]3[C:12](=[CH:11][C:10]([CH2:9][OH:8])=[C:19]([CH:20]=[O:21])[N:18]=3)[CH2:13][CH2:14][CH2:15]2)=[O:26])=[N:29][CH:30]=1)#[N:40]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 1317347846-(((tert-butyldimethylsilyl)oxy)methyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2×

Product 1

HCID 118036374N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-(hydroxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-(((tert-butyldimethylsilyl)oxy)methyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 74, 3.10 g, 5.43 mmol) in THF (40 ml) was treated with H2O (30 ml) followed by dropwise addition of conc. HCl (10 ml) and stirred for 40 min. The reaction mixture was quenched by addition of sat. aq. NaHCO3 (gas evolution) and then extracted with DCM (3×). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was treated with EtOAc (25 ml) and sonicated until a white suspension was obtained. Then, heptanes (25 ml) was added and the resulting suspension was filtered. The solid was washed with heptanes and dried under vacuum to give the title compound as a white solid.

Workup

  1. customThe reaction mixture was quenched by addition of sat. aq. NaHCO3 (gas evolution)
  2. extractionextracted with DCM (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was treated with EtOAc (25 ml)
  8. customsonicated until a white suspension
  9. customwas obtained
  10. filtrationthe resulting suspension was filtered
  11. washThe solid was washed with heptanes
  12. customdried under vacuum

Sources & evidence

ORD record
ord-f0b75ea160734f2f96415723fcf41549
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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