Sodium Hydroxide → HCID 71526353, compound

HRID 1755388Notes

Reaction equation

HRID 1755388 reaction equation
[C:1]([CH:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[C:14]([NH:16][C:17]3[C:18]4[N:19]([CH:33]=[CH:34][N:35]=4)[N:20]=[C:21]([C:23]4[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=4)[C:26]([O:28]C)=[O:27])[CH:22]=3)[CH:13]=[CH:12][CH:11]=2)[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>O1CCOCC1.O>[C:1]([CH:5]1[CH2:9][CH2:8][N:7]([C:10]2[N:15]=[C:14]([NH:16][C:17]3[C:18]4[N:19]([CH:33]=[CH:34][N:35]=4)[N:20]=[C:21]([C:23]4[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=4)[C:26]([OH:28])=[O:27])[CH:22]=3)[CH:13]=[CH:12][CH:11]=2)[CH2:6]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 71526355HCID 71526355, compound

Product 1

HCID 71526353HCID 71526353, compoundYield 99.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of methyl 3-(8-(6-(3-tert-butylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (55 mg, 0.11 mmol) in dioxane (5 mL) and water (5 mL) was added NaOH (50 mg, 1.25 mmol), then the mixture was heated to 40° C. with stirring for 3 h. The solution was concentrated in vacuo, washed with dichloromethane (10 mL×3), then water (10 mL) was added and the aqueous phase was adjusted to pH=2 by addition of 2M HCl. The solid formed was filtered and washed with water (1 mL) and MeOH (1 mL) to give 3-(8-(6-(3-tert-butylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (50 mg, 93%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 10.22 (s, 1H), 9.05 (s, 1H), 8.52 (s, 1H), 8.45 (s, 1H), 8.22 (d, 1H, J=8.1 Hz), 8.12 (d, 1H, J=7.5 Hz), 8.01 (s, 1H), 7.72 (t, 1H, J=7.5 Hz), 7.52 (t, 1H, J=7.8 Hz), 6.72 (d, 1H, J=7.5 Hz), 6.15 (d, 1H, J=8.4 Hz), 3.73-3.68 (m, 1H), 3.52-3.43 (m, 2H), 3.13 (t, 1H, J=10.5 Hz), 2.16-2.12 (m, 1H), 1.98-1.93 (m, 1H), 1.78-1.71 (m, 1H), 0.86 (s, 9H). LC-MS: [M+H]+, 457, tR=1.859 min, HPLC: 96.72% at 214 nm, 98.12% at 254 nm, tR=4.654 min.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. washwashed with dichloromethane (10 mL×3)
  3. additionwater (10 mL) was added
  4. additionthe aqueous phase was adjusted to pH=2 by addition of 2M HCl
  5. customThe solid formed
  6. filtrationwas filtered
  7. washwashed with water (1 mL) and MeOH (1 mL)

Sources & evidence

ORD record
ord-55c161ea1ad845e1aaafb47a059cccee
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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