Dichloromethane → (5)-Methyl 4-(3-(3-cyclopropyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-8-yl)-8-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]pyrazin-1-yl)benzoate

HRID 62468Notes

Reaction equation

HRID 62468 reaction equation
[CH3:1][O:2][C:3]1[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[N:9]([C:13]([C@@H:26]3[CH2:31][CH2:30][CH2:29][NH:28][C:27]3=S)=[N:14][C:15]=2[C:16]2[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=2)[CH:10]=[CH:11][N:12]=1.[CH:39]1([C:42]([NH:44][NH2:45])=O)[CH2:41][CH2:40]1.C(Cl)Cl>C1COCC1.[Hg](OC(C)=O)OC(C)=O>[CH:39]1([C:42]2[N:28]3[CH2:29][CH2:30][CH2:31][C@@H:26]([C:13]4[N:9]5[CH:10]=[CH:11][N:12]=[C:7]([NH:6][CH2:5][C:4]6[CH:33]=[CH:34][C:35]([O:37][CH3:38])=[CH:36][C:3]=6[O:2][CH3:1])[C:8]5=[C:15]([C:16]5[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=5)[N:14]=4)[C:27]3=[N:45][N:44]=2)[CH2:41][CH2:40]1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 81396CyclopropanecarbohydrazideHCID 90303997(S)-methyl 4-(8-((2,4-dimethoxybenzyl)amino)-3-(2-thioxopiperidin-3-yl)imidazo[1,5-a]pyrazin-1-yl)benzoate

Product 1

HCID 118559027(5)-Methyl 4-(3-(3-cyclopropyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-8-yl)-8-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]pyrazin-1-yl)benzoateYield 46%

Reagents, catalysts & solvents 2

HCID 16683746DiacetyloxymercuryCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (S)-methyl 4-(8-((2,4-dimethoxybenzyl)amino)-3-(2-thioxopiperidin-3-yl) imidazo[1,5-a]pyrazin-1-yl)benzoate (600 mg, 1.13 mmol) in THF (20 mL) was added cyclopropanecarbohydrazide (339 mg, 3.39 mmol) and Hg(OAc)2 (360 mg, 1.13 mmol). The mixture was stirred at RT for 20 minutes and then heated to 65° C. overnight. The reaction mixture was filtered and the filtrate was evaporated, the residue was purified by column chromatography on silica gel eluted with EA:DCM:THF=1:1:1 to give (S)-methyl 4-(3-(3-cyclopropyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridin-8-yl)-8-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]pyrazin-1-yl)benzoate (300 mg, yield 46%).

Workup

  1. temperatureheated to 65° C. overnight
  2. filtrationThe reaction mixture was filtered
  3. customthe filtrate was evaporated
  4. customthe residue was purified by column chromatography on silica gel
  5. washeluted with EA

Sources & evidence

ORD record
ord-f2703c28852a4b00a1ac3032714fde6d
Source dataset
uspto-grants-2016_09
Patent number
US09446130B2

Reaction notes

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