Sodium Hydroxide → 4-(1-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)piperidin-3-ylcarbamoyl)benzoic acid

HRID 1755398Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:37]=[CH:38][N:39]=3)[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([NH:24][C:25]([C:27]4[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=[O:32])=[CH:29][CH:28]=4)=[O:26])[CH2:19]3)[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10].[OH-].[Na+]>O1CCOCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:37]=[CH:38][N:39]=3)[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([NH:24][C:25]([C:27]4[CH:36]=[CH:35][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=4)=[O:26])[CH2:19]3)[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10]

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of methyl 4-(1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)piperidin-3-ylcarbamoyl)benzoate (50 mg, 0.09 mmol) and sodium hydroxide (50 mg, 1.25 mmol) in 1,4-dioxane (5 mL) and water (5 mL) was stirred at 40° C. for 3 h. The residue was concentrated in vacuo to ˜5 mL then adjusted pH to 2 with 1M HCl. The residue was concentrated and triturated with MeOH to give the product 4-(1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)piperidin-3-ylcarbamoyl)benzoic acid (15 mg, 31%) as yellow solid. 1H NMR (300 MHz, DMSO): δ 10.36 (s, 1H), 8.60 (d, 1H, J=7.2 Hz), 8.19 (s, 2H), 8.06-7.92 (m, 4 h), 7.45 (d, 1H, J=8.4 Hz), 6.95 (d, 1H, J=8.4 Hz), 4.18-4.07 (m, 3H), 3.99 (s, 3H), 3.91 (s, 3H), 3.07-2.99 (m, 2H), 1.98-1.88 (m, 2H), 1.70-1.64 (m, 2H). LC-MS: [M+H]+, 518, tR=1.295 min, HPLC: 95.24% at 214 nm, 95.25% at 254 nm, tR=4.981 min.

Workup

concentrationThe residue was concentrated in vacuo to ˜5 mL
concentrationThe residue was concentrated
customtriturated with MeOH

Sources & evidence

ORD record: ord-403ed9005de643adb37c6a29f21244a3
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09169259B2

Reaction notes

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