Sodium Hydroxide → HCID 71525709, compound

HRID 1755321Notes

Reaction equation

HRID 1755321 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]1[N:13]=[C:12]([NH:14][C:15]2[C:16]3[N:17]([CH:31]=[CH:32][N:33]=3)[N:18]=[C:19]([C:21]3[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=3)[C:24]([O:26]C)=[O:25])[CH:20]=2)[CH:11]=[CH:10][CH:9]=1.[OH-].[Na+]>O1CCOCC1.O>[OH:1][CH2:2][CH:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]1[N:13]=[C:12]([NH:14][C:15]2[C:16]3[N:17]([CH:31]=[CH:32][N:33]=3)[N:18]=[C:19]([C:21]3[CH:22]=[C:23]([CH:28]=[CH:29][CH:30]=3)[C:24]([OH:26])=[O:25])[CH:20]=2)[CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86682707HCID 86682707, compound

Product 1

HCID 71525709HCID 71525709, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of methyl 3-(8-(6-(2-(hydroxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate (185 mg, 0.416 mmol) in dioxane (5 mL) and water (4.5 mL) was added NaOH (167 mg, 4.16 mmol), then the mixture was heated to 40° C. with stirring for 4 h. The solution was concentrated in vacuo then water (10 mL) was added and the solution was washed with dichloromethane (10 mL×3). The aqueous layer was adjusted to pH=4 by addition of concentrated HCl. The solid formed was filtered to give 3-(8-(6-(2-(hydroxymethyl)pyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (0.096 g, 54%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 10.84 (s, 1H), 9.19 (s, 1H), 8.60 (s, 1H), 8.51 (s, 1H), 8.31 (s, 1H), 8.23 (d, 1H, J=7.5 Hz), 8.13 (d, 1H, J=7.5 Hz), 7.71 (t, 1H, J=7.8 Hz), 7.53 (t, 1H, J=7.8 Hz), 6.72 (d, 1H, J=7.5 Hz), 6.27 (d, 1H, J=8.1 Hz), 3.96 (brs, 2H), 3.61 (brs, 1H), 3.46-3.37 (m, 2H), 2.07-1.95 (m, 4 h). LC-MS: [M+H]+, 431, tR=1.459 min, HPLC: 99.27% at 214 nm, 99.49% at 254 nm, tR=5.08 min.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. additionwater (10 mL) was added
  3. washthe solution was washed with dichloromethane (10 mL×3)
  4. additionThe aqueous layer was adjusted to pH=4 by addition of concentrated HCl
  5. customThe solid formed
  6. filtrationwas filtered

Sources & evidence

ORD record
ord-539e5acebed94edf9778eb522056fa4a
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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