2-Methoxyethylamine → 1-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid[6-(2-methoxy-ethylsulfamoyl)-pyridin-3-ylmethyl]-amide

HRID 559630Notes

Reaction equation

HRID 559630 reaction equation
COC(=O)CC[S:6]([C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:17]([C:19]2[C:20]3[CH:27]=[N:26][N:25]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[C:21]=3[CH:22]=[N:23][CH:24]=2)=[O:18])=[CH:11][N:10]=1)(=[O:8])=[O:7].[O-]CC.[Na+].ClN1C(=O)CCC1=O.[CH3:48][O:49][CH2:50][CH2:51][NH2:52]>C1COCC1.C(O)C.[Cl-].[NH4+].CCOC(C)=O>[CH3:48][O:49][CH2:50][CH2:51][NH:52][S:6]([C:9]1[N:10]=[CH:11][C:12]([CH2:15][NH:16][C:17]([C:19]2[C:20]3[CH:27]=[N:26][N:25]([C:28]4[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=4)[C:21]=3[CH:22]=[N:23][CH:24]=2)=[O:18])=[CH:13][CH:14]=1)(=[O:7])=[O:8]

Participants

9

Reactant 4

HCID 80182-MethoxyethylamineHCID 31398ChlorosuccinimideHCID 2723922Sodium ethoxideHCID 59278313HCID 59278313, compound

Product 1

HCID 592783991-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid[6-(2-methoxy-ethylsulfamoyl)-pyridin-3-ylmethyl]-amide

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 3-[5-({[1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]-amino}-methyl)-pyridine-2-sulfonyl]-propionic acid methyl ester (100 mg, 0.2 mmol) in THF (5 mL) was added a freshly prepared 8% solution of sodium ethoxide (200 μL, 0.2 mmol) in ethanol. The mixture was stirred for 15 minutes and was monitored for the disappearance of starting material by TLC (EtOAc). The mixture was then concentrated to dryness under a stream of nitrogen. The mixture was again diluted with THF and then N-chlorosuccinimide (55 mg, 0.41 mmol) was added. After 15 minutes, 2-methoxyethylamine (0.100 mL, 1.15 mmol) was added in one portion. After 15 minutes, the mixture was diluted with saturated ammonium chloride and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (2×10 mL), dried over magnesium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography eluting with methanol-EtOAc (0:100, then 0.5:99.5, then 1:99, then 2:98). The material from the column was purified a second time by using preparative silica gel TLC eluting with methanol-EtOAc (1:9). The material from the plate was triturated with EtOAc-ether-hexanes to afford the title compound.

Workup

  1. concentrationThe mixture was then concentrated to dryness under a stream of nitrogen
  2. additionThe mixture was again diluted with THF
  3. waitAfter 15 minutes
  4. waitAfter 15 minutes
  5. extractionextracted with EtOAc (3×10 mL)
  6. washThe combined organic layers were washed with brine (2×10 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by silica gel chromatography
  11. washeluting with methanol-EtOAc (0:100
  12. customThe material from the column was purified a second time
  13. washeluting with methanol-EtOAc (1:9)
  14. customThe material from the plate was triturated with EtOAc-ether-hexanes

Sources & evidence

ORD record
ord-d98ea582d3c94204ad6306722f5d07c2
Source dataset
uspto-grants-2011_11
Patent number
US08063065B2

Reaction notes

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