Sodium Hydroxide → 3-(8-(6-(2,5-Dimethylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

HRID 1755378Notes

Reaction equation

[CH3:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH3:7])[N:3]1[C:8]1[N:13]=[C:12]([NH:14][C:15]2[C:16]3[N:17]([CH:31]=[CH:32][N:33]=3)[N:18]=[C:19]([C:21]3[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=3)[C:24]([O:26]C)=[O:25])[CH:20]=2)[CH:11]=[CH:10][CH:9]=1.[OH-].[Na+]>O1CCOCC1.O>[CH3:7][CH:4]1[CH2:5][CH2:6][CH:2]([CH3:1])[N:3]1[C:8]1[N:13]=[C:12]([NH:14][C:15]2[C:16]3[N:17]([CH:31]=[CH:32][N:33]=3)[N:18]=[C:19]([C:21]3[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=3)[C:24]([OH:26])=[O:25])[CH:20]=2)[CH:11]=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of methyl 3-(8-(6-(2,5-dimethylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (150 mg, 0.34 mmol) and NaOH (150 mg, 3.75 mmol) in 1,4-dioxane (5 mL) and water (5 mL) was stirred for 2 h at 40° C. Then the mixture was concentrated to 5 mL then adjusted to pH=2 with 2M HCl. The precipitate was filtered and the solid was washed with water (2 mL) and dichloromethane (3 mL) to give 3-(8-(6-(2,5-dimethylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (86 mg, 59%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 10.79 (s, 1H), 9.13 (s, 1H), 8.62 (s, 1H), 8.49 (s, 1H), 8.32-8.14 (m, 3H), 7.75 (t, 1H, J=7.8 Hz), 7.54 (t, 1H, J=8.1 Hz), 6.74 (d, 1H, J=7.8 Hz), 6.23 (d, 1H, J=8.7 Hz), 4.12 (s, 2H), 2.13-2.08 (m, 2H), 1.74-1.68 (m, 2H), 1.18 (s, 3H), 1.16 (s, 3H). LC-MS: [M+H]+, 429, tR=1.708 min, HPLC: 97.23% at 214 nm, 95.49% at 254 nm, tR=6.248 min.

Workup

concentrationThen the mixture was concentrated to 5 mL
filtrationThe precipitate was filtered
washthe solid was washed with water (2 mL) and dichloromethane (3 mL)

Sources & evidence

ORD record: ord-cf793c75c636464e83aee41cce9d0cf4
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169259B2

Reaction notes

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