Methanol → 3-(Methylamino)isoquinoline-6-carboxylic acid

HRID 880959Notes

Reaction equation

HRID 880959 reaction equation
FC(F)(F)[C:3]1[CH:4]=[C:5]([C:12]([OH:14])=[O:13])[CH:6]=[C:7]2[C:11]=1NN=[CH:8]2.Br[C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[CH:24]=[N:23][C:22]([NH:28][CH3:29])=[CH:21]2.O.O.[OH-].[Li+].[CH3:34]O>>[CH3:29][NH:28][C:22]1[N:23]=[CH:24][C:11]2[C:7]([CH:8]=1)=[CH:6][C:5]([C:12]([O:14][CH3:34])=[O:13])=[CH:4][CH:3]=2.[CH3:29][NH:28][C:22]1[N:23]=[CH:24][C:25]2[C:20]([CH:21]=1)=[CH:19][C:18]([C:12]([OH:14])=[O:13])=[CH:27][CH:26]=2

Participants

7

Reactant 5

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 674915516-bromo-N-methylisoquinolin-3-amineHCID 674918107-(trifluoromethyl)-1H-indazole-5-carboxylic acid

Product 2

HCID 674915683-(Methylamino)isoquinoline-6-carboxylic acidYield 89%HCID 67491618Methyl 3-(methylamino)isoquinoline-6-carboxylate

Procedure

Methyl 3-(methylamino)isoquinoline-6-carboxylate was prepared by a method analogous to that described in Step 3 of Intermediate 21, using 6-bromo-N-methylisoquinolin-3-amine. To the crude material (580 mg, 2.7 mmol) was added water (5 mL), methanol (5 mL), and lithium hydroxide monohydrate (300 mg, 7 mmol). The mixture was stirred at room temperature overnight. The reaction was concentrated and the residue was acidified to pH=5 with 1 N aqueous hydrochloric acid. The resulting residue was dried under vacuum and purified by reversed-phase HPLC to give the title compound (512 mg, 89%) as a white solid. 1H NMR (400 MHz, CD3OD, δ): 8.81 (s, 1H), 8.23 (s, 1H), 7.80 (d, 1H), 7.72 (d, 1H), 6.70 (s, 1H), 2.93 (s, 3H).

Workup

  1. concentrationThe reaction was concentrated
  2. customThe resulting residue was dried under vacuum
  3. custompurified by reversed-phase HPLC

Sources & evidence

ORD record
ord-7eff2a5e0dbb412ba275b1f2f22d0b95
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

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