Trifluoroacetic acid → (R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

HRID 1051814Notes

Reaction equation

HRID 1051814 reaction equation
C(O)(C(F)(F)F)=O.[CH:8]([C@H:11]1[N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14][N:13]2[C:24]3[CH:30]=[C:29]([S:31]([CH3:34])(=[O:33])=[O:32])[C:28]([C:35]([O:37][CH3:38])=[O:36])=[CH:27][C:25]=3[N:26]=[C:12]12)([CH3:10])[CH3:9]>C(Cl)Cl>[CH:8]([C@H:11]1[NH:16][CH2:15][CH2:14][N:13]2[C:24]3[CH:30]=[C:29]([S:31]([CH3:34])(=[O:33])=[O:32])[C:28]([C:35]([O:37][CH3:38])=[O:36])=[CH:27][C:25]=3[N:26]=[C:12]12)([CH3:10])[CH3:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89815749(R)-2-tert-butyl 8-methyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2,8 (1H)-dicarboxylate

Product 1

HCID 89815671(R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylateYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (4 mL) was added dropwise to a solution of containing (R)-2-tert-butyl 8-methyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2,8(1H)-dicarboxylate (2.0 g, 4.4 mmol) in DCM (20 mL) at rt over 2 min. The mixture was stirred at rt for 3 h. TLC showed the starting material was consumed completely. The solvent was removed in vacuo at 30° C., and then DCM (10 mL) was added. The mixture was neutralized with sat. aq. NaHCO3 to pH=7. The mixture was extracted with DCM (3×20 mL) and the combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under vacuum to afford (R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (1.5 g, 96.4% yield) as a white solid. LC-MS m/z 351.9 [M+H]+, 374.0 [M+Na]+. 1H NMR (CDCl3 300 MHz): δ 8.15 (s, 1H), 8.07 (s, 1H), 4.26-4.05 (m, 3H), 3.97 (s, 3H), 3.63-3.50 (m, 1H), 3.44 (s, 3H), 3.32-3.16 (m, 1H), 2.85-2.66 (m, 1H), 1.16 (d, J=6.9 Hz, 3H), 0.88 (d, J=6.6 Hz, 3H).

Workup

  1. customwas consumed completely
  2. customThe solvent was removed in vacuo at 30° C.
  3. additionDCM (10 mL) was added
  4. extractionThe mixture was extracted with DCM (3×20 mL)
  5. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-a8e0aa040164411f93563cd355d67ca4
Source dataset
uspto-grants-2016_07
Patent number
US09388190B2

Reaction notes

Loading…