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

HRID 1755348Notes

Reaction equation

HRID 1755348 reaction equation
[CH3:1][O:2][CH2:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]1[N:14]=[C:13]([NH:15][C:16]2[C:17]3[N:18]([CH:32]=[CH:33][N:34]=3)[N:19]=[C:20]([C:22]3[CH:23]=[C:24]([CH:29]=[CH:30][CH:31]=3)[C:25]([O:27]C)=[O:26])[CH:21]=2)[CH:12]=[CH:11][CH:10]=1.[OH-].[Na+]>O1CCOCC1.O>[CH3:1][O:2][CH2:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]1[N:14]=[C:13]([NH:15][C:16]2[C:17]3[N:18]([CH:32]=[CH:33][N:34]=3)[N:19]=[C:20]([C:22]3[CH:23]=[C:24]([CH:29]=[CH:30][CH:31]=3)[C:25]([OH:27])=[O:26])[CH:21]=2)[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86682721Methyl 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate

Product 1

HCID 715258983-(8-(6-(2-(Methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acidYield 28%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of methyl 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (0.155 g, 0.34 mmol) in dioxane (10 mL) and H2O (4 mL) was added NaOH (135 mg, 3.4 mmol) at 40° C. After 4 h the mixture was washed with ether (10 mL), the aqueous layer adjusted to pH=4 with concentrated HCl, then was concentrated and filtered. The collected solid was washed with ether and dried to afford 3-(8-(6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (0.037 g, 28% over two steps) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.80 (s, 1H), 8.54 (s, 1H), 8.20-8.08 (m, 3H), 7.72 (d, 1H, J=1.5 Hz), 7.59 (t, 1H, J=7.8 Hz), 7.45 (t, 1H, J=7.8 Hz), 6.31 (d, 1H, J=7.5 Hz), 6.17 (d, 1H, J=8.4 Hz), 4.21 (brs, 1H), 3.62-3.58 (m, 1H), 3.51-3.42 (m, 2H), 3.34-3.32 (m, 1H), 3.11 (s, 3H), 2.10-2.00 (m, 4 h). LC-MS: [M+H]+, 445, tR=1.714 min, HPLC: 95.14% at 214 nm, 95.00% at 254 nm, tR=5.9 min.

Workup

  1. washAfter 4 h the mixture was washed with ether (10 mL)
  2. concentrationwas concentrated
  3. filtrationfiltered
  4. washThe collected solid was washed with ether
  5. customdried

Sources & evidence

ORD record
ord-22d2627e08544bc79f8c2482e9bfbcdf
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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