Sodium Hydroxide → HCID 67315822, compound

HRID 533280Notes

Reaction equation

HRID 533280 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][CH2:15]/[CH:16]=[CH:17]/[C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([F:27])[CH:25]=2)[N:20]([CH2:28][CH2:29][CH2:30][O:31][C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:35]=[CH:34][CH:33]=2)[C:19]=1[C:42]([O:44]CC)=[O:43].[OH-:47].[Na+]>O1CCCC1.CO>[C:2]([C:10]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:4]([NH:3][CH2:12][CH2:13][CH2:14][CH2:15]/[CH:16]=[CH:17]/[C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([F:27])[CH:25]=2)[N:20]([CH2:28][CH2:29][CH2:30][O:31][C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:35]=[CH:34][CH:33]=2)[C:19]=1[C:42]([OH:44])=[O:43])=[O:11])([OH:47])=[O:1]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86630291(E)-ethyl 3-(6-(1,3-dioxoisoindolin-2-yl)hex-1-enyl)-5-fluoro-1-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylate

Product 1

HCID 67315822HCID 67315822, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of EXAMPLE 160A (531 mg) and potassium 1,3-dioxoisoindolin-2-ide (213 mg) in N,N-dimethylformamide (10 ml) was heated at 80° C. for 8 hours. The reaction was diluted with ethyl acetate and washed with water. The organic layer was dried over sodium sulfate and was concentrated. The residue was purified by flash chromatography, eluting with 0-100% ethyl acetate in dichloromethane to give (E)-ethyl 3-(6-(1,3-dioxoisoindolin-2-yl)hex-1-enyl)-5-fluoro-1-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylate. This ester was dissolved in a mixture of tetrahydrofuran and methanol and 5 equivalents of aqueous NaOH (10%) was added. The mixture was heated at 50° C. for 5 hours. The reaction mixture was concentrated and the residue was dissolved in dimethyl sulfoxide and trifluoroacetic acid-methanol (3:1), and purified by RPHPLC to provide the title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ 13.06 (s, 2H), 8.25 (t, J=5.52 Hz, 1H), 8.19 (dd, J=7.83, 1.38 Hz, 1H), 7.86 (dd, J=7.21, 1.99 Hz, 1H), 7.74 (dd, J=7.52, 1.38 Hz, 1H), 7.60-7.69 (m, 2H), 7.43-7.58 (m, 5H), 7.34-7.41 (m, 2H), 6.99-7.16 (m, 2H), 6.85 (d, J=7.36 Hz, 1H), 6.15-6.32 (m, 1H), 4.65-4.96 (m, 2H), 4.13 (t, J=5.68 Hz, 2H), 3.20-3.29 (m, 2H), 2.20-2.36 (m, 4H), 1.49-1.67 (m, 4H).

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in dimethyl sulfoxide
  4. customtrifluoroacetic acid-methanol (3:1), and purified by RPHPLC

Sources & evidence

ORD record
ord-540bd8fa554a49fe999a6166013e9c5c
Source dataset
uspto-grants-2014_10
Patent number
US08853209B2

Reaction notes

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