Sodium Carbonate → 7-[2-Chloro-3-(trifluoromethyl)benzyl]-3-(4-fluorophenyl)-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-one

HRID 576711Notes

Reaction equation

HRID 576711 reaction equation
Br[C:2]1[N:6]2[CH2:7][CH2:8][N:9]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[C:14]=3[Cl:23])[C:10](=[O:11])[C:5]2=[N:4][N:3]=1.[F:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:23][C:14]1[C:15]([C:19]([F:22])([F:21])[F:20])=[CH:16][CH:17]=[CH:18][C:13]=1[CH2:12][N:9]1[CH2:8][CH2:7][N:6]2[C:2]([C:28]3[CH:29]=[CH:30][C:25]([F:24])=[CH:26][CH:27]=3)=[N:3][N:4]=[C:5]2[C:10]1=[O:11]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 904024003-bromo-7-(2-chloro-3-(trifluoromethyl)benzyl)-6,7-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-one

Product 1

HCID 862792227-[2-Chloro-3-(trifluoromethyl)benzyl]-3-(4-fluorophenyl)-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-oneYield 46.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-bromo-7-(2-chloro-3-(trifluoromethyl)benzyl)-6,7-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-8(5H)-one (100 mg, 0.24 mmol) and 4-fluorophenylboronic acid (40 mg, 0.27 mmol) in dioxane (0.6 mL) was added 1M Na2CO3 (0.6 mL). The flask was purged with nitrogen for 10 minutes and Pd(PPh3)4 (14 mg, 0.012 mmol) was added at once. The flask was purged with nitrogen for an additional 5 minutes and then heated at 100° C. for 18 h. After cooling to rt, brine was added, and the mixture was extracted with EtOAc (×3). The combined organic extracts were dried (Na2SO4), filtered, and concentrated to give a brown solid. Purification by chromatography (SiO2; hexanes—100% EtOAc) afforded the desired product as a white solid (47 mg, 45%). MS (ESI): mass calcd. for C19H13ClF4N4O, 424.1; m/z found, 425.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 7.91-7.73 (m, 4H), 7.59-7.54 (m, 1H), 7.49-7.43 (m, 2H), 4.89 (s, 2H), 4.56-4.42 (m, 2H), 3.92-3.84 (m, 2H).

Workup

  1. customThe flask was purged with nitrogen for 10 minutes
  2. customThe flask was purged with nitrogen for an additional 5 minutes
  3. temperatureAfter cooling to rt
  4. additionbrine was added
  5. extractionthe mixture was extracted with EtOAc (×3)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a brown solid
  10. customPurification by chromatography (SiO2; hexanes—100% EtOAc)

Sources & evidence

ORD record
ord-fa67533ec23c48ee81ab84485ecc0460
Source dataset
uspto-grants-2015_05
Patent number
US09040534B2

Reaction notes

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