Trifluoroacetic acid → HCID 121480767, compound

HRID 1056382Notes

Reaction equation

HRID 1056382 reaction equation
C(OC(=O)[NH:7][C@H:8]([CH2:40][OH:41])[C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][C@H:14]([NH:18][C:19]2[C:28]([CH3:29])=[N:27][C:26]3[C:21](=[C:22]([C:30]4[NH:34][C:33]5[C@@H:35]([CH3:39])[NH:36][C:37](=[O:38])[C:32]=5[CH:31]=4)[CH:23]=[CH:24][CH:25]=3)[N:20]=2)[CH2:13]1)=[O:10])(C)(C)C.[C:43]([OH:49])([C:45]([F:48])([F:47])[F:46])=[O:44]>C(Cl)Cl>[F:46][C:45]([F:48])([F:47])[C:43]([OH:49])=[O:44].[NH2:7][C@H:8]([CH2:40][OH:41])[C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][C@H:14]([NH:18][C:19]2[C:28]([CH3:29])=[N:27][C:26]3[C:21](=[C:22]([C:30]4[NH:34][C:33]5[C@@H:35]([CH3:39])[NH:36][C:37](=[O:38])[C:32]=5[CH:31]=4)[CH:23]=[CH:24][CH:25]=3)[N:20]=2)[CH2:13]1)=[O:10]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89793923HCID 89793923, compound

Product 1

HCID 121480767HCID 121480767, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl((R)-3-hydroxy-1-(((1R,3S)-3-((3-methyl-8-((R)-6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinoxalin-2-yl)amino)cyclohexyl)amino)-1-oxopropan-2-yl)carbamate (491, 34 mg, 0.059 mmol) and TFA (0.45 mL, 5.89 mmol) in DCM (0.29 mL) was stirred at 0° C. to RT for 15 min. It was concentrated under reduced pressure. The crude product was dissolved in methanol and injected (3×1 mL) onto the Shimadzu preparative LC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 100% over 12 min) before the pure fractions were combined and concentrated via rotary evaporation to give (R)-2-amino-3-hydroxy-N-((1R,3S)-3-((3-methyl-8-((R)-6-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-2-yl)quinoxalin-2-yl)amino)cyclohexyl)propanamide 2,2,2-trifluoroacetate (497, 34 mg, 0.057 mmol, 98% yield) as a red oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.18-1.28 (m, 1H) 1.29-1.39 (m, 1H) 1.43-1.52 (m, 2H) 1.45 (d, J=6.65 Hz, 3H) 1.86 (d, J=10.56 Hz, 2H) 2.06-2.15 (m, 2H) 2.53 (s, 3H) 3.55-3.64 (m, 1H) 3.65-3.80 (m, 3H) 4.13-4.26 (m, 1H) 4.55 (q, J=6.85 Hz, 1H) 6.90 (d, J=8.02 Hz, 1H) 6.96 (d, J=1.37 Hz, 1H) 7.33 (t, J=7.73 Hz, 1H) 7.57-7.64 (m, 2H) 7.84 (d, J=7.43 Hz, 1H) 8.00-8.10 (m, 3H) 8.36 (d, J=7.82 Hz, 1H) 11.94 (s, 1H). MS (ESI, pos. ion) m/z: 478.1 (M+1).

Workup

  1. concentrationIt was concentrated under reduced pressure
  2. dissolutionThe crude product was dissolved in methanol
  3. customonto the Shimadzu preparative LC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 100% over 12 min)
  4. concentrationconcentrated via rotary evaporation

Sources & evidence

ORD record
ord-a5575a15c9ac49868184eb6c047fdd78
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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