Ammonia → 1-bromo-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo[1,5-a]pyrazin-8-amine

HRID 62461Notes

Reaction equation

HRID 62461 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([N:12]2[CH2:17][CH2:16][N:15]3[C:18]([C:21]([F:24])([F:23])[F:22])=[N:19][N:20]=[C:14]3[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7](Cl)[C:6]=12.[NH3:25].CC(O)C>>[Br:1][C:2]1[N:3]=[C:4]([N:12]2[CH2:17][CH2:16][N:15]3[C:18]([C:21]([F:24])([F:23])[F:22])=[N:19][N:20]=[C:14]3[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:25])[C:6]=12

Participants

4

Reactant 3

HCID 222AmmoniaHCID 3776IsopropanolHCID 903040957-(1-Bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine

Product 1

HCID 903040261-bromo-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo[1,5-a]pyrazin-8-amine

Conditions

Temperature
120 °C

Procedure

To a 75 ml sealed vessel was charged with 7-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (595 mg, 1.408 mmol) along with ammonia in IPA (2N, 0.704 ml, 1.408 mmol). The vessel was sealed with screw cap and heated in an oil bath of 120° C. for 18 hrs overnight. LC-MS showed complete conversion of starting material to product. The mixture was then cooled to room temperature, solid (gel) precipitated and was filtered, washed with IPA and dried to afford 1-bromo-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo[1,5-a]pyrazin-8-amine (250 mg). The filtrate was concentrated and the residue was purified by MPLC (12 g silica gel, 0 to 10% methanol in methylenechloride, 28 CV) to afford another batch of product. Totally 1-bromo-3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)imidazo[1,5-a]pyrazin-8-amine (386 mg, 0.957 mmol, 68.0% yield) was obtained. LC-MS: C12H10BrF3N8,402. found 403.08 [M+H]+, RT=1.09 min.

Workup

  1. customTo a 75 ml sealed vessel
  2. customThe vessel was sealed with screw
  3. customcap
  4. temperatureThe mixture was then cooled to room temperature
  5. customsolid (gel) precipitated
  6. filtrationwas filtered
  7. washwashed with IPA
  8. customdried

Sources & evidence

ORD record
ord-b2b8d769395b47c5873850d3543a416d
Source dataset
uspto-grants-2016_09
Patent number
US09446130B2

Reaction notes

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