Hydrochloric Acid → HCID 56925059, compound

HRID 661985Notes

Reaction equation

HRID 661985 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][NH:8][C:9]2[CH:21]=[C:20]3[C:12]([C:13]4[C:14]([C:25]5[CH:30]=[CH:29][CH:28]=[C:27]([N:31]6[CH2:39][C:38]7[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=7)[C:32]6=[O:40])[C:26]=5[CH3:41])=[CH:15][CH:16]=[C:17]([C:22]([NH2:24])=[O:23])[C:18]=4[NH:19]3)=[CH:11][CH:10]=2)[CH2:4][O:3]1.Cl.[OH-].[Na+]>C1COCC1>[OH:6][CH:5]([CH2:4][OH:3])[CH2:7][NH:8][C:9]1[CH:21]=[C:20]2[C:12]([C:13]3[C:14]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([N:31]5[CH2:39][C:38]6[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=6)[C:32]5=[O:40])[C:26]=4[CH3:41])=[CH:15][CH:16]=[C:17]([C:22]([NH2:24])=[O:23])[C:18]=3[NH:19]2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68747602HCID 68747602, compound

Product 1

HCID 56925059HCID 56925059, compoundYield 43.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 7-(((S)-2,2-dimethyl-1,3-dioxolan-4-yl)methylamino)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide (Example 66-15, 50 mg, 0.089 mmol) in THF (1 mL) was treated with 2 M hydrochloric acid (4.46 mL, 8.92 mmol) and the mixture was stirred at rt for 1 h. The mixture was made basic with 1 M aqueous sodium hydroxide and extracted twice with DCM. The combined organic phases, along with some insoluble precipitate, were dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from DCM to 90:9:1 DCM-methanol-28% aqueous ammonium hydroxide) to provide 7-(2,3-dihydroxypropylamino)-4-(2-methyl-3-(1-oxoisoindolin-2-yl)phenyl)-9H-carbazole-1-carboxamide as an orange solid (20 mg, 39%). 1H NMR (400 MHz, methanol-d4) δ 7.90 (1H, d, J=7.49 Hz), 7.79 (1H, d, J=7.77 Hz), 7.67-7.74 (2H, m), 7.58-7.62 (1H, m), 7.49-7.55 (2H, m), 7.42 (1H, dd, J=6.94, 1.94 Hz), 6.99 (1H, d, J=7.77 Hz), 6.86 (1H, d, J=8.32 Hz), 6.81 (1H, d, J=1.94 Hz), 6.45 (1H, dd, J=8.74, 1.80 Hz), 4.97 (2H, s), 3.88-3.93 (1H, m), 3.59-3.68 (2H, m), 3.36-3.39 (1H, m), 3.14-3.20 (1H, m), 1.95 (3H, s). Mass spectrum m/z 521.3 (M+H)+.

Workup

  1. extractionextracted twice with DCM
  2. customThe combined organic phases, along with some insoluble precipitate, were dried
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography (
  5. washeluting with a gradient from DCM to 90:9:1 DCM-methanol-28% aqueous ammonium hydroxide)

Sources & evidence

ORD record
ord-bcdac76d725245889bd1b6d38c3e9e79
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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