Hydrochloric Acid → HCID 56925059, compound

HRID 1811165Notes

Reaction equation

HRID 1811165 reaction equation
[CH3:1][C:2]1[C:7]([N:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:17])=[CH:6][CH:5]=[CH:4][C:3]=1[C:18]1[C:30]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[NH:23][C:22]=2[C:21]([C:31]([NH2:33])=[O:32])=[CH:20][CH:19]=1.Cl.[OH-:35].[Na+]>C1COCC1>[OH:35][CH:21]([CH2:31][OH:32])[CH2:22][NH:23][C:26]1[CH:25]=[C:24]2[C:29]([C:30]3[C:18]([C:3]4[CH:4]=[CH:5][CH:6]=[C:7]([N:8]5[CH2:16][C:15]6[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=6)[C:9]5=[O:17])[C:2]=4[CH3:1])=[CH:19][CH:20]=[C:21]([C:31]([NH2:33])=[O:32])[C:22]=3[NH:23]2)=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86663003HCID 86663003, compound

Product 1

HCID 56925059HCID 56925059, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 74(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 (1 H, d, J=7.49 Hz), 7.79 (1 H, d, J=7.77 Hz), 7.67-7.74 (2 H, m), 7.58-7.62 (1 H, m), 7.49-7.55 (2 H, m), 7.42 (1 H, dd, J=6.94, 1.94 Hz), 6.99 (1H, d, J=7.77 Hz), 6.86 (1 H, d, J=8.32 Hz), 6.81 (1 H, d, J=1.94 Hz), 6.45 (1 H, dd, J=8.74, 1.80 Hz), 4.97 (2 H, s), 3.88-3.93 (1 H, m), 3.59-3.68 (2 H, m), 3.36-3.39 (1 H, m), 3.14-3.20 (1 H, m), 1.95 (3 H, 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-0e938a3a9e2f4c63a5dcfcafdb374e14
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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