Water → HCID 178461718, compound

HRID 2098235Notes

Reaction equation

HRID 2098235 reaction equation
[CH3:1][C@@H:2]([OH:7])[CH2:3][C@H:4]([OH:6])[CH3:5].[F:8][C:9]([F:39])([F:38])[C:10]1[CH:11]=[C:12]([C:16]2[CH:37]=[CH:36][C:19]3[NH:20][C:21]([NH:23][C:24]([C:26]4[N:27]=[C:28]5[CH:33]=[CH:32][C:31](Cl)=[N:30][N:29]5[CH:35]=4)=[O:25])=[N:22][C:18]=3[CH:17]=2)[CH:13]=[CH:14][CH:15]=1.O>CN(C=O)C>[F:39][C:9]([F:8])([F:38])[C:10]1[CH:11]=[C:12]([C:16]2[CH:37]=[CH:36][C:19]3[NH:20][C:21]([NH:23][C:24]([C:26]4[N:27]=[C:28]5[CH:33]=[CH:32][C:31]([O:6][C@H:4]([CH3:5])[CH2:3][C@H:2]([OH:7])[CH3:1])=[N:30][N:29]5[CH:35]=4)=[O:25])=[N:22][C:18]=3[CH:17]=2)[CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 962WaterHCID 27236832,4-Pentanediol, (-)-HCID 178522475HCID 178522475, compound

Product 1

HCID 178461718HCID 178461718, compoundYield 48.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2R,4R)-(−)-pentanediol (31.2 mg) in dry DMF (1 mL) NaH (12 mg, 60% dispersion in mineral oil) was added, and the mixture was stirred at room temperature for 20 minutes under nitrogen. To this mixture 6-chloro-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-trifluoromethyl-phenyl)-1H-benzoimidazol-2-yl]-amide (45.6 mg) was added. The reaction was monitored by LCMS until substantially complete. Then, 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 to obtain 6-((1R,3R)-3-hydroxy-1-methyl-butoxy)-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-trifluoromethyl-phenyl)-1H-benzoimidazol-2-yl]-amide (25.2 mg). LCMS (m/z): 526.1. 1H NMR (400 MHz, CDCl3) δ 8.39 (1H, s) 7.89 (1H, s) 7.45-7.85 (7H, m) 6.79 (1H, d) 5.42 (1H, ddd) 3.95 (1H, d) 2.18 (1H, brs) 1.91 (1H, ddd) 1.69-1.79 (1H, m) 1.44 (3H, d) 1.26 (3H, d)

Workup

  1. stirringthe reaction mixture was stirred for 10 minutes
  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

Sources & evidence

ORD record
ord-0da401df64db48fc916c12901a6b43aa
Source dataset
uspto-grants-2013_05
Patent number
US08450354B2

Reaction notes

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