Hydrochloric Acid → 2-(8-((5-Cyanopyridin-2-yl)carbamoyl)-2-formyl-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acetic acid

HRID 1778084Notes

Reaction equation

HRID 1778084 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]([N:12]2[C:21]3[N:20]=[C:19]([CH:22](OC)[O:23]C)[C:18]([CH2:27][C:28]([O:30]C(C)(C)C)=[O:29])=[CH:17][C:16]=3[CH2:15][CH2:14][CH2:13]2)=[O:11])=[N:7][CH:8]=1)#[N:2].Cl.C([O-])(O)=O.[Na+]>C1COCC1.O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]([N:12]2[C:21]3[N:20]=[C:19]([CH:22]=[O:23])[C:18]([CH2:27][C:28]([OH:30])=[O:29])=[CH:17][C:16]=3[CH2:15][CH2:14][CH2:13]2)=[O:11])=[N:7][CH:8]=1)#[N:2]

Participants

6

Reactant 3

HCID 313Hydrochloric Acid3×HCID 516892Sodium BicarbonateHCID 118036371Tert-butyl 2-(8-((5-cyanopyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acetate2×

Product 1

HCID 1180365622-(8-((5-Cyanopyridin-2-yl)carbamoyl)-2-formyl-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of tert-butyl 2-(8-((5-cyanopyridin-2-yl)carbamoyl)-2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acetate (intermediate 48, 33 mg, 0.071 mmol) in THF (1 ml) and H2O (1 ml) was added conc. HCl (0.5 ml). The suspension was stirred at room temperature for 2 days, then conc. HCl (0.5 ml) was added and the reaction mixture was stirred at room temperature for 2 days. Then conc. HCl (0.5 ml) was added and the reaction mixture was stirred for 1 h. The reaction mixture was poured into sat. aq. NaHCO3 and extracted with DCM (5×). The aqueous phase was acidified with conc. HCl and extracted with DCM (3×). All aq. and organic phases were combined and evaporated. The residue was subjected to reverse phase chromatography (13 g C18 cartridge, 0.1% TFA in water/acetonitrile 90:10 to 0:100). The product containing fractions were lyophilized to give the title compound as a colorless powder.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 2 days
  2. stirringthe reaction mixture was stirred for 1 h
  3. extractionextracted with DCM (5×)
  4. extractionextracted with DCM (3×)
  5. customevaporated
  6. additionThe product containing fractions

Sources & evidence

ORD record
ord-3534f786d5584ff58cd670683134fcb1
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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