Acetic Anhydride → HCID 59375109, compound

HRID 1811115Notes

Reaction equation

HRID 1811115 reaction equation
[NH2:1][CH2:2][C:3]1[CH:15]=[C:14]2[C:6]([C:7]3[C:8]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[CH2:33][C:32]6[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=6)[C:26]5=[O:34])[C:20]=4[CH3:35])=[CH:9][CH:10]=[C:11]([C:16]([NH2:18])=[O:17])[C:12]=3[NH:13]2)=[CH:5][CH:4]=1.[C:36](OC(=O)C)(=[O:38])[CH3:37]>C1COCC1>[C:36]([NH:1][CH2:2][C:3]1[CH:15]=[C:14]2[C:6]([C:7]3[C:8]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[CH2:33][C:32]6[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=6)[C:26]5=[O:34])[C:20]=4[CH3:35])=[CH:9][CH:10]=[C:11]([C:16]([NH2:18])=[O:17])[C:12]=3[NH:13]2)=[CH:5][CH:4]=1)(=[O:38])[CH3:37]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 59375043HCID 59375043, compound

Product 1

HCID 59375109HCID 59375109, compoundYield 36.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of crude 7-(aminomethyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 33-1, 60 mg, 0.065 mmol) and TEA (23 μL, 0.163 mmol) in THF (1.3 mL) was treated with acetic anhydride (7.4 μL, 0.078 mmol) and the mixture was stirred at rt overnight. The mixture was concentrated and the residue was purified by preparative HPLC. The appropriate effluent fractions were concentrated and the residue was partitioned between NaHCO3 (aq) and EtOAc. The organic phase was washed with brine, dried and concentrated to provide 7-(acetamidomethyl)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide as an off-white solid (12 mg, 36%). 1H NMR (400 MHz, DMSO-d6) δ 11.51 (1 H, s), 8.29-8.45 (1 H, m), 8.18 (1 H, br. s.), 8.01 (1H, d, J=7.9 Hz), 7.81 (1 H, d, J=7.5 Hz), 7.69 (2 H, d, J=4.0 Hz), 7.60-7.65 (2 H, m), 7.57 (1 H, ddd, J=7.9, 4.2, 4.0 Hz), 7.50 (2 H, t, J=7.8 Hz), 7.34 (1 H, dd, J=7.7, 1.1 Hz), 6.94-7.06 (2 H, m), 6.87 (1 H, dd, J=8.3, 1.4 Hz), 4.90-5.04 (2 H, m), 4.35 (2H, t, J=5.2 Hz), 1.89 (3 H, s), 1.84 (3 H, s). Mass spectrum m/z 503.2 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by preparative HPLC
  3. concentrationThe appropriate effluent fractions were concentrated
  4. customthe residue was partitioned between NaHCO3 (aq) and EtOAc
  5. washThe organic phase was washed with brine
  6. customdried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2435698f2a254f019b838f4591d05c0f
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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