Sodium Hydroxide → 4-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

HRID 1755315Notes

Reaction equation

HRID 1755315 reaction equation
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:30]=[CH:31][N:32]=3)[N:17]=[C:18]([C:20]3[CH:29]=[CH:28][C:23]([C:24]([O:26]C)=[O:25])=[CH:22][CH:21]=3)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1.[OH-].[Na+]>O1CCOCC1.O>[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:30]=[CH:31][N:32]=3)[N:17]=[C:18]([C:20]3[CH:29]=[CH:28][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=3)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 71525614Methyl 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate

Product 1

HCID 715256154-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acidYield 87.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of methyl 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (220 mg, 0.51 mmol) in dioxane (10 mL) and water (9 mL) was added NaOH (200 mg, 5 mmol), then the mixture was heated to 40° C. with stirring for 4 h. The solution was concentrated to approximately 10 mL in vacuo and washed with dichloromethane (10 mL×3). Water (10 mL) was added and the solution was adjusted to pH=4 by the addition of concentrated HCl. The solid formed was filtered to give 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (0.185 g, 87%) as a light yellow solid. 1H NMR (300 MHz, DMSO): δ 9.72 (s, 1H), 8.82 (s, 1H), 8.23 (s, 1H), 8.09-8.02 (m, 3H), 7.69 (s, 1H), 7.44 (t, 1H, J=7.5 Hz), 6.73 (d, 1H, J=7.5 Hz), 6.08 (d, 1H, J=8.4 Hz), 4.23-4.20 (m, 1H), 3.58-3.56 (m, 2H), 2.08-1.97 (m, 3H), 1.68 (s, 1H), 1.12 (d, 1H, J=6.3 Hz). LC-MS: [M+H]+, 415, tR=1.652 min, HPLC: 98.19% at 214 nm, 97.87% at 254 nm, tR=5.967 min.

Workup

  1. concentrationThe solution was concentrated to approximately 10 mL in vacuo
  2. washwashed with dichloromethane (10 mL×3)
  3. additionWater (10 mL) was added
  4. additionthe solution was adjusted to pH=4 by the addition of concentrated HCl
  5. customThe solid formed
  6. filtrationwas filtered

Sources & evidence

ORD record
ord-94e0e8a3e2564e689fd1810d1623a388
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

Loading…