Ammonia → HCID 56597868, compound

HRID 1522367Notes

Reaction equation

HRID 1522367 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.[N:30]1(C(OC(C)(C)C)=O)[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.N>C(Cl)Cl.C(Cl)(Cl)Cl.O>[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]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:3]=1)=[O:15]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 702EthanolHCID 143452tert-Butyl piperazine-1-carboxylateHCID 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 56597868HCID 56597868, compoundYield 55%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a 10 mL microwave vial equipped with stir bar were 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 (0.060 g, 0.160 mmol), ethanol (1.5 mL), and 1,1-dimethylethyl 1-piperazinecarboxylate (0.299 g, 1.605 mmol). The stirring suspension was placed onto heat block and heated at 120° C. for 18 h, and then irradiated (microwave) at 160° C. for 2 hr. The contents were cooled to room temperature, diluted into water (40 mL), and then adjusted to pH 6-7 and stirred for 15 min. The contents were filtered, washed with water, and then dried in hi-vac oven at 50° C. for 5 hr. The collected solid (52 mg) was dissolved in CH2Cl2/TFA (3 mL, 2:1) and stirred at room temperature for 2 hr. The volatiles were removed in vacuo to afford a residue which was then dissolved in CH2Cl2 and 10% 2M Ammonia (in methanol) in Chloroform. The crude product was purified by silica gel chromatography (eluent: gradient of 10% 2M Ammonia (in Methanol/Chloroform) and Dichloromethane). The isolated solid was dried in vacuum oven at 45° C. for 18 hr. to afford the final product as 38 mg (55% yield). LCMS E-S (M+H)=423.9. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43 (d, J=6.82 Hz, 6 H), 2.08-2.24 (m, 6 H), 2.75-2.89 (m, 4 H), 3.53-3.64 (m, 4 H), 4.34 (d, J=4.80 Hz, 2H), 4.98 (quin, J=6.69 Hz, 1 H), 5.89 (s, 1 H), 7.10 (s, 1 H), 8.00 (s, 1 H), 8.65 (t, J=4.93 Hz, 1 H), 11.55 (br. s., 1 H).

Workup

  1. customTo a 10 mL microwave vial equipped
  2. temperatureonto heat block
  3. customirradiated (microwave) at 160° C. for 2 hr
  4. temperatureThe contents were cooled to room temperature
  5. stirringstirred for 15 min
  6. filtrationThe contents were filtered
  7. washwashed with water
  8. customdried in hi-vac oven at 50° C. for 5 hr
  9. dissolutionThe collected solid (52 mg) was dissolved in CH2Cl2/TFA (3 mL, 2:1)
  10. stirringstirred at room temperature for 2 hr
  11. customThe volatiles were removed in vacuo
  12. customto afford a residue which
  13. customThe crude product was purified by silica gel chromatography (eluent: gradient of 10% 2M Ammonia (in Methanol/Chloroform) and Dichloromethane)
  14. customThe isolated solid was dried in vacuum oven at 45° C. for 18 hr

Sources & evidence

ORD record
ord-81077895db28415a85b91f81d1667c39
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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