Sodium Carbonate → Methyl 3-amino-4-(3-(1,3-dioxoisoindolin-2-yl)propoxy)benzo[b]thiophene-2-carboxylate

HRID 1685107Notes

Reaction equation

HRID 1685107 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][O:15][C:16]1[CH:23]=[CH:22][CH:21]=[C:20](F)[C:17]=1[C:18]#[N:19].[C:25]([O:29][CH3:30])(=[O:28])[CH2:26][SH:27].C(=O)([O-])[O-].[Na+].[Na+]>CO.O>[NH2:19][C:18]1[C:17]2[C:16]([O:15][CH2:14][CH2:13][CH2:12][N:3]3[C:2](=[O:1])[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[C:4]3=[O:11])=[CH:23][CH:22]=[CH:21][C:20]=2[S:27][C:26]=1[C:25]([O:29][CH3:30])=[O:28]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 16907Methyl ThioglycolateHCID 672652932-(3-(1,3-Dioxoisoindolin-2-yl)propoxy)-6-fluorobenzonitrile

Product 1

HCID 67265156Methyl 3-amino-4-(3-(1,3-dioxoisoindolin-2-yl)propoxy)benzo[b]thiophene-2-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of EXAMPLE 14A (0.5 g, 1.54 mmol), methyl thioglycolate (217 μL, 2.31 mmol), and sodium carbonate (653 mg, 6.16 mmol), was heated in methanol (7.7 mL) at 70° C. for 21 hours. The mixture was cooled, diluted with water, and the precipitate filtered and dried. The crude product was purified by flash chromatography on silica gel using a gradient of 0-2% methanol in dichloromethane to provide the title compound as an 85% pure mixture with unreacted EXAMPLE 14A. 1H NMR (DMSO-d6) δ 7.79-7.88 (m, 5H), 7.33-7.44 (m, 2H), 6.97 (s, 1H), 6.86 (dd, J=7.8, 1.0 Hz, 1H), 4.23 (t, J=5.8 Hz, 2H), 3.80 (t, J=6.8 Hz, 2H), 3.77 (s, 3H), 2.17 (quin, J=6.1 Hz, 2H).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationthe precipitate filtered
  3. customdried
  4. customThe crude product was purified by flash chromatography on silica gel using a gradient of 0-2% methanol in dichloromethane

Sources & evidence

ORD record
ord-e85420a1426a4fe2aae6036fb3a4531d
Source dataset
uspto-grants-2012_04
Patent number
US08148384B2

Reaction notes

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