1,4-Dioxane → 7-(3-Chloro-1,2,4-triazin-5-yl)-8-methyl-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine

HRID 510189Notes

Reaction equation

HRID 510189 reaction equation
O1CCOCC1.[Cl:7][C:8]1[N:9]=[N:10][CH:11]=[C:12](Cl)[N:13]=1.Cl.[CH3:16][CH:17]1[NH:22][CH2:21][CH2:20][N:19]2[C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][CH:25]=[C:18]12.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Cl:7][C:8]1[N:9]=[N:10][CH:11]=[C:12]([N:22]2[CH2:21][CH2:20][N:19]3[C:23]([C:26]([F:29])([F:27])[F:28])=[N:24][CH:25]=[C:18]3[CH:17]2[CH3:16])[N:13]=1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 122649333,5-Dichloro-1,2,4-triazineHCID 1176286328-Methyl-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine hydrochloride

Product 1

HCID 1176285957-(3-Chloro-1,2,4-triazin-5-yl)-8-methyl-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a Dioxane (12.0 ml) solution of 3,5 dichloro-1,2,4-triazine (780 mg, 5.20 mmol) was added 8-methyl-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine hydrochloride (CA, 1257 mg, 5.20 mmol) followed by diisopropylethylamine (2.73 ml, 15.60 mmol). Dichloromethane (2 mL) was added to solubilize the reaction. The reaction was stirred for 2 hrs at RT and then diluted with DCM. The reaction was washed with saturated sodium bicarbonate then brine, dried with sodium sulfate and concentrated to anoil. Purification of the oil on Biotage Normal Phase system (DCM:MeOH, 0-9% B) to afford the product as a solid, 1-17, (1.2 g, 71.7%). LRMS (ESI) m/z 319.1 [(M+H)+; calcd for C11H10ClF3N6: 319.1].

Workup

  1. customthe reaction
  2. washThe reaction was washed with saturated sodium bicarbonate
  3. dry with materialbrine, dried with sodium sulfate
  4. concentrationconcentrated to anoil
  5. customPurification of the oil on Biotage Normal Phase system (DCM:MeOH, 0-9% B)

Sources & evidence

ORD record
ord-efea71f9d372488ba64ec679fdc0d038
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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