Trifluoroacetic acid → HCID 89783902, compound

HRID 1056336Notes

Reaction equation

HRID 1056336 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH:11]([C:20]1[NH:21][C:22]([C:32]2[CH:41]=[CH:40][CH:39]=[C:38]3[C:33]=2[N:34]=[C:35]([NH:43][C:44]([CH3:47])([CH3:46])[CH3:45])[C:36]([CH3:42])=[N:37]3)=[CH:23][C:24]=1C(OC(C)(C)C)=O)[NH:12][C:13]([O:15]C(C)(C)C)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>C(Cl)Cl>[CH2:1]([O:8][CH2:9][CH2:10][CH:11]1[C:20]2[NH:21][C:22]([C:32]3[CH:41]=[CH:40][CH:39]=[C:38]4[C:33]=3[N:34]=[C:35]([NH:43][C:44]([CH3:47])([CH3:46])[CH3:45])[C:36]([CH3:42])=[N:37]4)=[CH:23][C:24]=2[C:13](=[O:15])[NH:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 118512039HCID 118512039, compound

Product 1

HCID 89783902HCID 89783902, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

To a solution of tert-butyl 2-(3-(benzyloxy)-1-((tert-butoxycarbonyl)amino)propyl)-5-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (1.28 g, 1.98 mmol) in 20 mL of DCM at RT was added TFA (5 mL) and the dark red solution was heated in an oil bath at 40° C. for 4 h. It was concentrated under reduced pressure. 5 mL of toluene was added to the residue and concentrated to dryness again. The brown amorphous solid was stirred in 15 mL of hexanes and the liquid was decanted. The brown residue was treated with 5 mL of DMF and 30 mL of DCM, cooled at 0° C., and added DIPEA (2.06 mL, 11.88 mmol) followed by (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (1.28 g, 2.47 mmol). It was stirred at 0° C. for 10 min followed by RT for 15 min, then diluted with 50 mL of DCM. The mixture was washed sequentially with 5 mL of water, 5 mL of 0.5 N NaOH, and 5 mL of brine. The DCM solution was concentrated. The residue was purified on a silica gel column (50-100% EtOAc in DCM followed by 5% MeOH in DCM) to give 6-(2-(benzyloxy)ethyl)-2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (0.65 g, 1.38 mmol, 70% yield) as a brown crystalline solid. m/z (ESI, +ve) 470.0 (M+H)+.

Workup

  1. concentrationIt was concentrated under reduced pressure
  2. addition5 mL of toluene was added to the residue
  3. concentrationconcentrated to dryness again
  4. customthe liquid was decanted
  5. additionThe brown residue was treated with 5 mL of DMF and 30 mL of DCM
  6. temperaturecooled at 0° C.
  7. stirringIt was stirred at 0° C. for 10 min
  8. washThe mixture was washed sequentially with 5 mL of water, 5 mL of 0.5 N NaOH, and 5 mL of brine
  9. concentrationThe DCM solution was concentrated
  10. customThe residue was purified on a silica gel column (50-100% EtOAc in DCM followed by 5% MeOH in DCM)

Sources & evidence

ORD record
ord-ca67176fbf21425f8b21bf13c93d0e34
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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