Methanol → 4-[6-Amino-5-(5-chloro-8-methoxyisoquinolin-3-yl)-pyridin-3-yl]benzoic acid

HRID 1926324Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12](OC)=[O:13])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:18]1[N:19]=[CH:20][C:21]2[C:26]([CH:27]=1)=[C:25]([Cl:28])[CH:24]=[CH:23][C:22]=2F.[OH-:30].[Na+].[CH3:32][OH:33]>O>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([OH:30])=[O:13])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:18]1[N:19]=[CH:20][C:21]2[C:26]([CH:27]=1)=[C:25]([Cl:28])[CH:24]=[CH:23][C:22]=2[O:33][CH3:32]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of methyl 4-[6-amino-5-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-3-yl]-benzoate (0.13 g, 0.32 mmol) in methanol (5 mL) and water (0.5 mL) was added NaOH (0.24 g, 6 mmol), and the mixture was heated at 50° C. for 16 h. The solvents were evaporated at reduced pressure, and the residue was neutralized with acetic acid. The solid formed was filtered off and dried in vacuo to give the title compound. 1H NMR (400 MHz, DMSO-d6): δ=12.82 (very brs, 1H), 9.63 (s, 1H), 8.51 (d, J=2.4 Hz, 1H), 8.35 (s, 1H), 8.31 (d, J=2.4 Hz, 1H), 8.03-7.98 & 7.90-7.85 (AA′BB′, 4H), 7.92 (d, J=8.0 Hz, 1H), 7.27 (brs, 2H), 7.15 (d, J=8.0 Hz, 1H), 4.07 (s, 3H). MS(ES+): m/z=406.08/408.03 (100/53) [MH+]. HPLC: tR=3.00 min (polar—5 min, ZQ3).

Workup

customThe solvents were evaporated at reduced pressure
customThe solid formed
filtrationwas filtered off
customdried in vacuo

Sources & evidence

ORD record: ord-5082e1fb7b044c0cbcd2b95aa06209eb
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178668B2

Reaction notes

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