Diisopropylethylamine → 6-iodo-N-methyl-2-phenylpyrazolo[1,5-a]pyridine-3-carboxamide

HRID 44022Notes

Reaction equation

HRID 44022 reaction equation
[I:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:8]=[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:10]=2[C:11](O)=[O:12])[CH:7]=1.O[N:21]1[C:25]2N=CC=CC=2N=N1.Cl.CN.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>C(OC(=O)C)C.CN(C)C=O.ClCCl>[I:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([N:8]=[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:10]=2[C:11]([NH:21][CH3:25])=[O:12])[CH:7]=1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 592337716-Iodo-2-phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid

Product 1

HCID 592337926-iodo-N-methyl-2-phenylpyrazolo[1,5-a]pyridine-3-carboxamideYield 90%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 250 mL round-bottomed flask equipped with a magnetic stir bar was charged 6-iodo-2-phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid (200 mg, 0.549 mmol), 1-Hydroxy-7-azabenzotriazole (74.8 mg, 0.549 mmol), methylamine hydrochloride (55.6 mg, 0.824 mmol), diisopropylethylamine (671 μL, 3.84 mmol), dichloromethane (5000 μL) and dimethylforamide (500 μL). To this yellow solution 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (147 mg, 0.769 mmol) was added. The reaction was stirred at room temperature for six hours and diluted with ethylacetate (200 mL). The organic portion was washed 5× with 0.5N hydrochloric acid, 1× saturated sodium bicarbonate and 2× brine. The organic portion was dried over magnesium sulfate. The solvent was removed by rotory evaporation. The residue was place under vacuum overnight to give a white solid (130 mg, 90%). 1H NMR (500 MHz, MeOD) δ ppm 2.87 (m, 3H) 7.51 (m, 3H) 7.63 (dd, J=9.31, 1.37 Hz, 1H) 7.76 (m, 3H) 8.94 (s, 1H). LCMS: 1.8 minutes, M+1=378.

Workup

  1. customTo a 250 mL round-bottomed flask equipped with a magnetic stir bar
  2. washThe organic portion was washed 5× with 0.5N hydrochloric acid, 1× saturated sodium bicarbonate and 2× brine
  3. dry with materialThe organic portion was dried over magnesium sulfate
  4. customThe solvent was removed by rotory evaporation
  5. customunder vacuum overnight

Sources & evidence

ORD record
ord-41d16c6ad135470f89fbc1c02ef707e7
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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