Phosphorus oxychloride → HCID 67976348, compound

HRID 706700Notes

Reaction equation

HRID 706700 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][N:14]3[C:17]([C:20]([OH:22])=O)=[CH:18][N:19]=[C:13]3[CH:12]=2)[CH2:4][CH2:3]1.P(Cl)(Cl)([Cl:25])=O.[NH2:28][C:29]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:30]=1[CH:31]=[N:32][N:33]2[CH2:38][C:39]1[C:40](=[O:46])[N:41]([CH3:45])[CH:42]=[CH:43][CH:44]=1>CC(N(C)C)=O>[ClH:25].[ClH:25].[CH3:45][N:41]1[CH:42]=[CH:43][CH:44]=[C:39]([CH2:38][N:33]2[C:34]3[C:30](=[C:29]([NH:28][C:20]([C:17]4[N:14]5[CH:15]=[CH:16][C:11]([O:10][CH2:9][CH2:8][N:5]6[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]6)=[CH:12][C:13]5=[N:19][CH:18]=4)=[O:22])[CH:37]=[CH:36][CH:35]=3)[CH:31]=[N:32]2)[C:40]1=[O:46]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 672527437-(2-(4-Methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylic acidHCID 67976165HCID 67976165, compound

Product 1

HCID 67976348HCID 67976348, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

7-(2-(4-Methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylic acid (0.072 g, 0.21 mmol) was added to DMA (1 mL) and cooled to 0° C. Phosphorus oxychloride (0.038 mL, 0.41 mmol) was added and the reaction mixture was stirred for 30 minutes. 3-((4-Amino-1H-indazol-1-yl)methyl)-1-methylpyridin-2 (1H)-one (0.035 g, 0.14 mmol) was added and the reaction mixture was stirred at ambient temperature overnight. The reaction was concentrated and then suspended in 2 M LiOH (2 mL). The resulting mixture was stirred for 30 minutes and then diluted with CHCl3 and saturated aqueous NaHCO3. The layers were separated and the aqueous phase was extracted with CHCl3. The combined organic layers were dried over MgSO4 and concentrated. The residue was purified by preparative thin layer chromatography (1:6 2.3 M NH3 in MeOH:CH2Cl2), added to MeOH (2 mL) and reacted with HCl (2 M in Et2O, 2 mL). The mixture was stirred for 60 minutes and then concentrated. The resulting solids were suspended in Et2O and filtered to provide N-(1-((1-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride (0.035 g, 41% yield) as a solid. MS (ES+APCI) m/z=541 (M+H-2HCl).

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature overnight
  2. concentrationThe reaction was concentrated
  3. stirringThe resulting mixture was stirred for 30 minutes
  4. additiondiluted with CHCl3 and saturated aqueous NaHCO3
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with CHCl3
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by preparative thin layer chromatography (1:6 2.3 M NH3 in MeOH:CH2Cl2)
  10. additionadded to MeOH (2 mL)
  11. customreacted with HCl (2 M in Et2O, 2 mL)
  12. stirringThe mixture was stirred for 60 minutes
  13. concentrationconcentrated
  14. filtrationfiltered

Sources & evidence

ORD record
ord-ed62c9ecef134e31a221bdedc5fa0994
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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