Sodium Hydroxide → 3-(8-(6-(3-Aza-bicyclo[3.1.0]hexan-3-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

HRID 1755329Notes

Reaction equation

HRID 1755329 reaction equation
[CH:1]12[CH2:6][CH:5]1[CH2:4][N:3]([C:7]1[N:12]=[C:11]([NH:13][C:14]3[C:15]4[N:16]([CH:30]=[CH:31][N:32]=4)[N:17]=[C:18]([C:20]4[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=4)[C:23]([O:25]C)=[O:24])[CH:19]=3)[CH:10]=[CH:9][CH:8]=1)[CH2:2]2.[OH-].[Na+]>O1CCOCC1.O>[CH:1]12[CH2:6][CH:5]1[CH2:4][N:3]([C:7]1[N:12]=[C:11]([NH:13][C:14]3[C:15]4[N:16]([CH:30]=[CH:31][N:32]=4)[N:17]=[C:18]([C:20]4[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=4)[C:23]([OH:25])=[O:24])[CH:19]=3)[CH:10]=[CH:9][CH:8]=1)[CH2:2]2

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86682713HCID 86682713, compound

Product 1

HCID 715257133-(8-(6-(3-Aza-bicyclo[3.1.0]hexan-3-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acidYield 68.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of methyl 3-(8-(6-(3-aza-bicyclo[3.1.0]hexan-3-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (70 mg, 0.16 mmol) in dioxane (5 mL) and water (4 mL) was added NaOH (63 mg, 1.6 mmol), then the mixture was heated to 40° C. with stirring for 4 h. The solution was concentrated in vacuo. Water (10 mL) was added to the residue and was washed with dichloromethane (15 mL×3). The aqueous layer was adjusted to pH=4 by the addition of concentrated HCl. The solid formed was collected by filtration to give 3-(8-(6-(3-aza-bicyclo[3.1.0]hexan-3-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (0.045 g, 67%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.88 (s, 1H), 8.92 (s, 1H), 8.54 (s, 1H), 8.31-8.10 (m, 3H), 7.80-7.72 (m, 2H), 7.47 (s, 1H), 6.76 (s, 1H), 6.11 (s, 1H), 3.71-3.54 (m, 4 h), 1.72 (s, 2H), 0.78 (s, 1H), 0.22 (s, 1H). LC-MS: [M+H]+, 413, tR=1.665 min, HPLC: 95.09% at 214 nm, 95% at 254 nm, tR=5.831 min.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. additionWater (10 mL) was added to the residue
  3. washwas washed with dichloromethane (15 mL×3)
  4. additionThe aqueous layer was adjusted to pH=4 by the addition of concentrated HCl
  5. customThe solid formed
  6. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-66ca6cb6fd684e64b9b98a68a3d1c80b
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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