Acetic Anhydride → HCID 89793911, compound

HRID 1056375Notes

Reaction equation

HRID 1056375 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([NH:8][C:9]2[C:10]([CH3:29])=[N:11][C:12]3[C:17]([N:18]=2)=[C:16]([C:19]2[NH:23][C:22]4[C@@H:24]([CH3:28])[NH:25][C:26](=[O:27])[C:21]=4[CH:20]=2)[CH:15]=[CH:14][CH:13]=3)[CH2:3]1.[C:30](OC(=O)C)(=[O:32])[CH3:31].C(N(C(C)C)C(C)C)C>C(Cl)Cl>[CH3:29][C:10]1[C:9]([NH:8][C@H:4]2[CH2:5][CH2:6][CH2:7][C@@H:2]([NH:1][C:30](=[O:32])[CH3:31])[CH2:3]2)=[N:18][C:17]2[C:12]([N:11]=1)=[CH:13][CH:14]=[CH:15][C:16]=2[C:19]1[NH:23][C:22]2[C@@H:24]([CH3:28])[NH:25][C:26](=[O:27])[C:21]=2[CH:20]=1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 89783660HCID 89783660, compound

Product 1

HCID 89793911HCID 89793911, compoundYield 59.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of (R)-2-(3-(((1S,3R)-3-aminocyclohexyl)amino)-2-methylquinoxalin-5-yl)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (483) (29 mg, 0.074 mmol), acetic anhydride (35.0 μL, 0.37 mmol), and N-ethyl-N-isopropylpropan-2-amine (91 μL, 0.52 mmol) in DCM (743 μL) was stirred at RT for 30 min when mostly product was observed via LCMS. The reaction mixture was diluted with DCM (100 mL), added to a separatory funnel, and washed with saturated aqueous sodium bicarbonate (2×75 mL); the organic layer was separated, dried over Na2SO4, and concentrated. The crude product in DCM was loaded onto the column and was purified via automated flash chromatography (silica gel) with 100% DCM to 8% 2 M ammonia in MeOH/DCM to give 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)acetamide (486, 19 mg, 0.044 mmol, 59% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.08-1.20 (m, 1H) 1.20-1.32 (m, 1H) 1.42 (d, J=6.65 Hz, 3H) 1.44-1.52 (m, 2H) 1.78 (s, 3H) 1.80-1.90 (m, 2H) 2.11 (br. s., 2H) 2.53 (s, 3H) 3.58-3.71 (m, 1H) 4.04-4.17 (m, 1H) 4.54 (q, J=6.59 Hz, 1H) 6.87 (d, J=7.63 Hz, 1H) 6.95 (d, J=1.57 Hz, 1H) 7.33 (t, J=7.82 Hz, 1H) 7.59 (dd, J=8.02, 1.37 Hz, 1H) 7.62 (s, 1H) 7.81-7.88 (m, 2H) 11.99 (s, 1H). MS (ESI, pos. ion) m/z: 433.1 (M+1).

Workup

  1. additionadded to a separatory funnel
  2. washwashed with saturated aqueous sodium bicarbonate (2×75 mL)
  3. customthe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customwas purified

Sources & evidence

ORD record
ord-32486665d8884bfeb540305493ae0403
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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