Sodium Hydroxide → N-(5-(2-Amino-3-(3-fluorophenyl)imidazo[1,2-b]pyridazin-6-yl)-2-chloropyridin-3-yl)methanesulfonamide

HRID 1162455Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([C:14]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=4)=[C:15]([NH:17]C(=O)C)[N:16]=3)[N:13]=2)=[CH:4][C:3]=1[NH:28][S:29]([CH3:32])(=[O:31])=[O:30].[OH-].[Na+].C([O-])(=O)C.[Na+]>CO>[NH2:17][C:15]1[N:16]=[C:11]2[CH:10]=[CH:9][C:8]([C:5]3[CH:4]=[C:3]([NH:28][S:29]([CH3:32])(=[O:30])=[O:31])[C:2]([Cl:1])=[N:7][CH:6]=3)=[N:13][N:12]2[C:14]=1[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a 4-mL vial was added N-(6-(6-chloro-5-(methylsulfonamido)pyridin-3-yl)-3-(3-fluorophenyl)imidazo[1,2-b]pyridazin-2-yl)acetamide (TFA salt) (Example 22) (0.025 g, 0.042 mmol), methanol (2.5 mL) and sodium hydroxide (0.250 mL, 2.5 mmol, 10 M). The mixture was stirred at 60° C. for 15 h. After cooling to rt, the mixture was neutralized with pH 4.8 buffer (Teknova, 3 M sodium acetate solution pH adjusted to 4.8). The solution was partially concentrated to remove the MeOH. The solution was filtered and the filtercake was washed with water (2×) and then dried under vacuum to afford the title compound as a yellow solid (0.016 g, 86%). MS (ESI, positive ion) m/z: 433 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.68 (s, 3H), 5.90 (s, 2H), 7.08-7.13 (m, 1H), 7.51-7.58 (m, 2H), 7.76-7.81 (m, 1H), 7.84 (d, J=9.2 Hz, 1H), 8.00 (d, J=8.0 Hz, 1H), 8.06 (s, 1H), 8.15 (d, J=2.2 Hz, 1H), 11.93 (br s, 1H).

Workup

temperatureAfter cooling to rt
concentrationThe solution was partially concentrated
customto remove the MeOH
filtrationThe solution was filtered
washthe filtercake was washed with water (2×)
customdried under vacuum

Sources & evidence

ORD record: ord-725042fa7d264b3b96e7a83409c50e9e
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820665B2

Reaction notes

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