Hydrogen Bromide → HCID 59375128, compound

HRID 1811156Notes

Reaction equation

HRID 1811156 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[N:9]([C:15]1[C:16]([CH3:48])=[C:17]([C:21]3[CH:33]=[CH:32][C:31]([C:34](=[O:36])[NH2:35])=[C:30]4[C:22]=3[C:23]3[CH:24]=[CH:25][C:26]([NH:37]C(=O)OCC5C=CC=CC=5)=[CH:27][C:28]=3[NH:29]4)[CH:18]=[CH:19][CH:20]=1)[CH2:8]2)([CH3:4])([CH3:3])[CH3:2].Br>C(Cl)Cl>[NH2:37][C:26]1[CH:27]=[C:28]2[C:23]([C:22]3[C:21]([C:17]4[CH:18]=[CH:19][CH:20]=[C:15]([N:9]5[CH2:8][C:7]6[C:11](=[CH:12][CH:13]=[C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[CH:6]=6)[C:10]5=[O:14])[C:16]=4[CH3:48])=[CH:33][CH:32]=[C:31]([C:34]([NH2:35])=[O:36])[C:30]=3[NH:29]2)=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 66605751HCID 66605751, compound

Product 1

HCID 59375128HCID 59375128, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of benzyl 5-(3-(5-tert-butyl-1-oxoisoindolin-2-yl)-2-methylphenyl)-8-carbamoyl-9H-carbazol-2-ylcarbamate (Example 51-4, 65 mg, 0.102 mmol) in hydrogen bromide (30-35% in acetic acid, 5 mL, 27.6 mmol) was stirred at rt for 1.5 h. The mixture was diluted with DCM and concentrated. The residue was dissolved in DCM containing a small amount of methanol and the solution was mixed with 1 M aqueous sodium hydroxide. The organic phase was separated, washed with water, dried and concentrated, and the residue was triturated with hexane. The residue was purified by column chromatography (eluting with a gradient from 97:2.7:0.3 to 90:9:1 DCM-methanol-28% aqueous ammonium hydroxide) to provide 7-amino-4-(3-(5-tert-butyl-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-carbazole-1-carboxamide as a white solid (Example 54-3, 45 mg, 88%) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 10.32 (1 H, s), 7.89 (1 H, d, J=8.35 Hz), 7.57 (1 H, d, J=7.91 Hz), 7.49-7.55 (2 H, m), 7.35-7.47 (3 H, m), 7.04 (1 H, d, J=7.47 Hz), 6.93 (1 H, d, J=8.35 Hz), 6.74 (1 H, d, J=1.76 Hz), 6.46 (1 H, dd, J=8.57, 1.98 Hz), 4.79 (2 H, d, J=2.20 Hz), 3.84 (2 H, br. s.), 1.96 (3 H, s), 1.40 (9 H, s). Mass spectrum m/z 503.3 (M+H)+. Also obtained was 7-amino-6-bromo-4-(3-(5-tert-butyl-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-carbazole-1-carboxamide as a white solid (Example 54-4, 5 mg, 8%). 1H NMR (400 MHz, chloroform-d) δ 10.34 (1 H, s), 7.89 (1 H, d, J=7.91 Hz), 7.53-7.59 (3 H, m), 7.44-7.48 (2 H, m), 7.35 (1 H, dd, J=5.71, 3.08 Hz), 7.05-7.08 (2 H, m), 6.84 (1 H, s), 4.83 (2 H, s), 4.22 (2 H, br. s.), 1.95 (3 H, s), 1.40 (9 H, s). Mass spectrum m/z 581, 583 (M+H)+.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in DCM containing a small amount of methanol
  3. additionthe solution was mixed with 1 M aqueous sodium hydroxide
  4. customThe organic phase was separated
  5. washwashed with water
  6. customdried
  7. concentrationconcentrated
  8. customthe residue was triturated with hexane
  9. customThe residue was purified by column chromatography (
  10. washeluting with a gradient from 97:2.7:0.3 to 90:9:1 DCM-methanol-28% aqueous ammonium hydroxide)

Sources & evidence

ORD record
ord-d2f263675bf4419d832b0f866788a98b
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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