Water → HCID 178522483, compound

HRID 2098243Notes

Reaction equation

HRID 2098243 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:30]=[CH:29][C:12]3[NH:13][C:14]([NH:16][C:17]([C:19]4[N:20]=[C:21]5[CH:26]=[CH:25][C:24](Cl)=[N:23][N:22]5[CH:28]=4)=[O:18])=[N:15][C:11]=3[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[NH:31]1[CH2:36][CH2:35][CH:34]([OH:37])[CH2:33][CH2:32]1.O>CN1CCCC1=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:30]=[CH:29][C:12]3[NH:13][C:14]([NH:16][C:17]([C:19]4[N:20]=[C:21]5[CH:26]=[CH:25][C:24]([N:31]6[CH2:36][CH2:35][CH:34]([OH:37])[CH2:33][CH2:32]6)=[N:23][N:22]5[CH:28]=4)=[O:18])=[N:15][C:11]=3[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 79341Piperidin-4-olHCID 178522482HCID 178522482, compound

Product 1

HCID 178522483HCID 178522483, compoundYield 39.9%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-chloro-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-chloro-5-fluoro-phenyl)-1H-benzoimidazol-2-yl]-amide (0.07 g) in N-methylpyrrolidone (1 mL), was added piperidin-4-ol (0.08 g) and the mixture was heated to 80° C. for 12 hours. After cooling the reaction mixture, 10 mL of water was added and the reaction mixture was stirred for 10 minutes. The reaction was then filtered through a fine fritted funnel and the crude product was washed with water. After air drying, purified by column chromatography (pre-packed silica column) using a gradient of 0 to 10% 2M ammonia-methanol in DCM to obtain 6-(4-hydroxy-piperidin-1-yl)-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-chloro-5-fluoro-phenyl)-1H-benzoimidazol-2-yl]-amide (32 mg). LCMS (m/z): 506.7. 1H NMR (400 MHz, DMSO-d6) δ 8.64 (1H, s) 7.93 (1H, d) 7.80-7.86 (1H, m) 7.48-7.65 (4H, m) 7.35-7.43 (2H, m) 4.79 (1H, br. s.) 3.95 (2H, ddd) 3.70-3.80 (1H, m) 3.18-3.45 (2H, m) 1.79-1.90 (2H, m) 1.39-1.53 (2H, m).

Workup

  1. additionwas added
  2. filtrationThe reaction was then filtered through a fine fritted funnel
  3. washthe crude product was washed with water
  4. customAfter air drying
  5. custompurified by column chromatography (pre-packed silica column)

Sources & evidence

ORD record
ord-58251ebb59ec42a98cb14f8e970d11af
Source dataset
uspto-grants-2013_05
Patent number
US08450354B2

Reaction notes

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