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

HRID 2046021Notes

Reaction equation

HRID 2046021 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]1[CH:14]1[CH2:16][CH:15]1[C:17](O)=O)[CH3:2].CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:33][N:34]1[C:39]([CH3:40])=[CH:38][N:37]=[C:36]([CH3:41])[C:35]1=[NH2+:42].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>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]1[CH:14]1[CH2:16][CH:15]1[C:17]1[N:42]=[C:35]2[C:36]([CH3:41])=[N:37][CH:38]=[C:39]([CH3:40])[N:34]2[N:33]=1)[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 711437752-(1-ethyl-4-phenyl-1H-imidazol-2-yl)cyclopropanecarboxylic acidHCID 178425979HCID 178425979, compound

Product 1

HCID 711438022-(2-(1-Ethyl-4-phenyl-1H-imidazol-2-yl)cyclopropyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazineYield 50.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(1-ethyl-4-phenyl-1H-imidazol-2-yl)cyclopropanecarboxylic acid (103 mg, 0.4 mmol) in DMF (3.0 mL) was added 1-amino-3,6-dimethylpyrazin-2(1H)-iminium 2,4,6-trimethylbenzenesulfonate (135 mg, 0.400 mmol) followed by O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (128 mg, 0.400 mmol) and triethylamine (0.277 mL, 2.000 mmol) at rt. After 1 h stirring at rt, the reaction mixture was heated at 70° C. for 15 h. The crude was purified by prep HPLC using Phenomenex column and MeOH—H2O-TFA as eluent (25% to 100% over 12 min gradient; 40 mL/min flow). Collected the pure fractions and removed solvent. Prepared HCl salt by adding MeOH (3 mL) and 1.0 M HCl (3 mL) and removing solvent. Obtained 2-(2-(1-ethyl-4-phenyl-1H-imidazol-2-yl)cyclopropyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine, 1.0HCl (85 mg, 0.202 mmol, 50.6% yield) as a white solid. 1H NMR (500 MHz, METHANOL-d4) δ 8.13 (d, J=0.9 Hz, 1H), 7.99 (s, 1H), 7.80-7.78 (m, 1H), 7.77-7.75 (m, 1H), 7.58-7.50 (m, 2H), 7.40-7.22 (m, 1H), 4.38 (q, J=7.3 Hz, 2H), 3.29-3.25 (m, 1H), 3.10-3.08 (m, 1H), 2.98 (s, 3H), 2.85 (s, 3H), 2.21-2.18 (m, 2H), 1.60 (t, J=7.4 Hz, 3H); MS (ESI) 359 (M+H); Rf=1.99 (Condition A).

Workup

  1. temperaturethe reaction mixture was heated at 70° C. for 15 h
  2. customThe crude was purified by prep HPLC
  3. custom(25% to 100% over 12 min gradient; 40 mL/min flow)
  4. customCollected the pure fractions
  5. customremoved solvent
  6. additionPrepared HCl salt by adding MeOH (3 mL) and 1.0 M HCl (3 mL)
  7. customremoving solvent

Sources & evidence

ORD record
ord-74e966b6c4a1401f8ed4b73a44ea00ad
Source dataset
uspto-grants-2013_11
Patent number
US08592423B2

Reaction notes

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