Triethylamine → 5,8-Dimethyl-2-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)cyclopropyl)-[1,2,4]triazolo[1,5-a]pyrazine

HRID 2046019Notes

Reaction equation

HRID 2046019 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:4]=[C:3]1[CH:13]1[CH2:15][CH:14]1[C:16](O)=O.CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:32][N:33]1[C:38]([CH3:39])=[CH:37][N:36]=[C:35]([CH3:40])[C:34]1=[NH2+:41].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[CH3:39][C:38]1[N:33]2[N:32]=[C:16]([CH:14]3[CH2:15][CH:13]3[C:3]3[N:2]([CH3:1])[CH:6]=[C:5]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)[N:4]=3)[N:41]=[C:34]2[C:35]([CH3:40])=[N:36][CH:37]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 711437792-(1-methyl-4-phenyl-1H-imidazol-2-yl)cyclopropanecarboxylic acidHCID 178425979HCID 178425979, compound

Product 1

HCID 711438395,8-Dimethyl-2-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)cyclopropyl)-[1,2,4]triazolo[1,5-a]pyrazineYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(1-methyl-4-phenyl-1H-imidazol-2-yl)cyclopropanecarboxylic acid (70 mg, 0.289 mmol) in DMF (2.0 mL) was added 1-amino-3,6-dimethylpyrazin-2(1H)-iminium 2,4,6-trimethylbenzenesulfonate (98 mg, 0.289 mmol) followed by O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (93 mg, 0.289 mmol) and triethylamine (0.040 mL, 0.289 mmol) at rt. After 2 h stirring at rt, the reaction mixture was stirred at 70° C. for 12 h. The crude was purified by prep HPLC using Phenomenex column and MeOH—H2O-TFA as eluent (20% to 100% over 12 min gradient; flow: 40 mL/min). Collected the pure fractions and removed solvent. Obtained 5,8-dimethyl-2-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)cyclopropyl)-[1,2,4]triazolo[1,5-a]pyrazine in 44% yield. Prepared hydrochloride salt by adding 1.0 M HCl (3 mL) and MeOH (3 mL) and removing solvent. 1H NMR (500 MHz, METHANOL-d4) δ 6.63 (s, 1H), 6.24 (s, 1H), 6.15-6.11 (m, 2H), 5.90-5.85 (m, 2H), 5.84-5.79 (m, 1H), 2.33 (s, 3H), 1.74-1.71 (m, 1H), 1.50-1.44 (m, 4H), 1.28 (s, 3H), 0.63-0.58 (m, 1H), 0.56-0.51 (m, 1H); MS (ESI) 345 (M+H); Rf=1.61 (Condition A).

Workup

  1. stirringthe reaction mixture was stirred at 70° C. for 12 h
  2. customThe crude was purified by prep HPLC
  3. custom(20% to 100% over 12 min gradient; flow: 40 mL/min)
  4. customCollected the pure fractions
  5. customremoved solvent
  6. additionPrepared hydrochloride salt by adding 1.0 M HCl (3 mL) and MeOH (3 mL)
  7. customremoving solvent

Sources & evidence

ORD record
ord-07a38da8277a4ca9b9e7247659a4c7c4
Source dataset
uspto-grants-2013_11
Patent number
US08592423B2

Reaction notes

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