Ethanol → HCID 56598002, compound

HRID 475982Notes

Reaction equation

HRID 475982 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.C(O)C.[CH2:30]([NH2:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([NH:37][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:3]=1)=[O:15]

Participants

5

Reactant 3

HCID 702EthanolHCID 7504BenzylamineHCID 565974256-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Product 1

HCID 56598002HCID 56598002, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
135 °C

Procedure

To a 10 mL microwave vial were sequentially added 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.100 g, 0.267 mmol), ethanol (2.0 mL) and then benzylamine (0.350 mL, 3.21 mmol) via syringe at once. The sealed contents were irradiated at 140° C. for 3 hr. The contents were transferred to a heat block and heated at 135° C. for 16 hr., and then at 145° C. for an additional 12 h. After cooling to room temperature, the contents were diluted with CH2Cl2 and pre-absorbed onto silica gel. The crude product was purified by silica gel chromatography (dry loaded, eluent; gradient of 5-80% DCM and chloroform containing 10% 2M Ammonia (in methanol)). The isolated solid was triturated with MTBE, filtered, and washed with additional MTBE. The collected solid was dried in vacuum oven at 45° C. overnight to afford the final product as 0.067 g (55%). LCMS E-S (M+H)=445.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38 (d, J=6.57 Hz, 6H), 2.12 (s, 3H), 2.20 (s, 3H), 4.31 (d, J=5.05 Hz, 2H), 4.56 (d, J=6.06 Hz, 2H), 4.92 (quin, J=6.69 Hz, 1H), 5.88 (s, 1H), 6.69 (s, 1H), 7.18-7.25 (m, 1H), 7.26-7.35 (m, 2H), 7.35-7.43 (m, 2H), 7.77 (t, J=5.94 Hz, 1H), 7.83 (s, 1H), 8.47 (t, J=5.05 Hz, 1H), 11.55 (br. s., 1H).

Workup

  1. customThe sealed contents were irradiated at 140° C. for 3 hr
  2. temperatureAfter cooling to room temperature
  3. custompre-absorbed onto silica gel
  4. customThe crude product was purified by silica gel chromatography (dry loaded, eluent; gradient of 5-80% DCM and chloroform containing 10% 2M Ammonia (in methanol))
  5. customThe isolated solid was triturated with MTBE
  6. filtrationfiltered
  7. washwashed with additional MTBE
  8. customThe collected solid was dried in vacuum oven at 45° C. overnight

Sources & evidence

ORD record
ord-2326d179976a45eeb392721eba3ba141
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

Loading…