Hydrochloric Acid → HCID 86656329, compound

HRID 1630357Notes

Reaction equation

HRID 1630357 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([Cl:25])[N:23]=3)[N:18]=[CH:17][C:16]=2[C:26]([O:28]CC)=[O:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.[Li+].[OH-].Cl>O.C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([Cl:25])[N:23]=3)[N:18]=[CH:17][C:16]=2[C:26]([OH:28])=[O:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 887MethanolHCID 3939Lithium HydroxideHCID 86656330HCID 86656330, compound

Product 1

HCID 86656329HCID 86656329, compoundYield 90.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Crude ethyl 4-(1-(tert-butoxycarbonyl)piperidin-4-ylamino)-6-chloro-1,5-naphthyridine-3-carboxylate (54) (240.8 g, 554 mmol) was suspended in a 1:1:1 mixture of MeOH:THF:H2O (500 mL each) and LiOH (39.8 g, 1.66 mol, 3 eq) was added. The mixture was maintained at rt and monitored by LCMS. After consumption of starting material, the volatiles were removed under vacuum and the resultant solution was neutralized by the addition of 6N HCl (˜3 eq). The mixture was then carefully acidified to pH 3-5 with 5N HCl (aq). The resultant slurry was then filtered and the precipitate was rinsed with water and then methanol. The resultant precipitate was dried in a vac-oven overnight, to give 203.6 g (83%, over two steps) of 4-(1-(tert-butoxycarbonyl)piperidin-4-ylamino)-6-chloro-1,5-naphthyridine-3-carboxylic acid (55).

Workup

  1. customAfter consumption of starting material
  2. customthe volatiles were removed under vacuum
  3. filtrationThe resultant slurry was then filtered
  4. washthe precipitate was rinsed with water
  5. dry with materialThe resultant precipitate was dried in a vac-oven overnight

Sources & evidence

ORD record
ord-98f4fe5459584295acb52cc39b77356f
Source dataset
uspto-grants-2014_07
Patent number
US08791131B2

Reaction notes

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