3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride → 2,2-Dimethyl-1-{2-[3-(3-trifluoromethyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-phenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-propan-1-one

HRID 1677433Notes

Reaction equation

HRID 1677433 reaction equation
I[C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]3[C:16]([C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:15][N:14](COCC[Si](C)(C)C)[C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.Cl.[F:32][C:33]([F:44])([F:43])[C:34]1[N:38]2[CH2:39][CH2:40][NH:41][CH2:42][C:37]2=[N:36][N:35]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.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>[CH3:19][C:18]([CH3:20])([CH3:21])[C:17]([C:16]1[C:10]2[C:11](=[N:12][CH:13]=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([N:41]4[CH2:40][CH2:39][N:38]5[C:34]([C:33]([F:44])([F:32])[F:43])=[N:35][N:36]=[C:37]5[CH2:42]4)[CH:3]=3)[N:9]=2)[NH:14][CH:15]=1)=[O:22]

Participants

6

Reactant 3

HCID 119613713-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochlorideHCID 23676156Sodium t-butoxideHCID 595405201-[2-(3-iodo-phenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one

Product 1

HCID 595406102,2-Dimethyl-1-{2-[3-(3-trifluoromethyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-phenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-propan-1-oneYield 33.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1-[2-(3-iodo-phenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (0.083 g, 0.16 mmol), 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride (0.05 g, 0.24 mmol), Pd(PPh3)4 (0.023 g, 0.02 mmol) and sodium t-butoxide (0.046 g, 0.48 mmol) in toluene (2 mL) were heated under an argon atmosphere in a microwave oven at 90° C. for 1 h. After cooling to room temperature, the reaction mixture was directly purified by flash column chromatography on silica gel with a mixture of 28% aqueous ammonium hydroxide:methanol:DCM (1:10:60) in DCM (20% to 80% gradient over 30 min) to give 25 mg of the desired product as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 8.84 (s, 1H), 8.48 (s, 1H), 8.23 (s, 1H), 7.95 (br s, 1H), 7.74 (d, J=7.7 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 5.74 (s, 2H), 4.80 (s, 2H), 4.37 (t, J=5.3 Hz, 2H), 3.91 (t, J=5.4 Hz, 2H), 3.66 (dd, J=8.2 Hz, 2H), 1.62 (s, 9H), 0 (s, 9H); MS [M+H]+: 600.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture was directly purified by flash column chromatography on silica gel with a mixture of 28% aqueous ammonium hydroxide:methanol:DCM (1:10:60) in DCM (20% to 80% gradient over 30 min)

Sources & evidence

ORD record
ord-8304fcb3b2e64685a6c28a33a1b5abc0
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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