Methylhydrazine → 6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80803Notes

Reaction equation

HRID 80803 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[CH2:32][N:31]([C:33](=O)[CH2:34][C:35](=O)[CH:36]([CH3:38])[CH3:37])[CH2:30][CH2:29][C:5]=2[N:6]=[C:7]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[C:11]([CH3:28])=[CH:12][N:13]3[S:18]([C:21]2[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=2)(=[O:20])=[O:19])[N:8]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=S)=CC=1.[CH3:63][NH:64][NH2:65]>C1COCC1.ClCCl.O>[CH:36]([C:35]1[CH:34]=[C:33]([N:31]2[CH2:30][CH2:29][C:5]3[N:6]=[C:7]([C:9]4[CH:17]=[CH:16][CH:15]=[C:14]5[C:10]=4[C:11]([CH3:28])=[CH:12][N:13]5[S:18]([C:21]4[CH:22]=[CH:23][C:24]([CH3:25])=[CH:26][CH:27]=4)(=[O:19])=[O:20])[N:8]=[C:3]([O:2][CH3:1])[C:4]=3[CH2:32]2)[N:64]([CH3:63])[N:65]=1)([CH3:37])[CH3:38]

Participants

7

Reactant 3

HCID 6061MethylhydrazineHCID 87949Lawesson's reagentHCID 866902601-(4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpentane-1,3-dione

Product 1

HCID 712405966-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 1-(4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpentane-1,3-dione (350 mg, 0.624 mmol) in THF (3.3 mL), in a 2-5 mL microwave vial, was added Lawesson's reagent (278 mg, 0.687 mmol) and methyl hydrazine (0.049 mL, 0.94 mmol). The vessel was immediately sealed and heated via microwave irradiation at 120° C. for 10 minutes. The reaction was then cooled to room temperature and diluted with dichloromethane and water. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. The resulting residue was purified via silica gel flash chromatography (45-67% ethyl acetate/heptanes) to provide 6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. MS (ESI+) m/z 571.4 (M+H)+.

Workup

  1. customThe vessel was immediately sealed
  2. temperatureThe reaction was then cooled to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted two additional times with dichloromethane
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified via silica gel flash chromatography (45-67% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-330158821a2f4cd4a7b5c34f6818b039
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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