Pyridine → methyl(5-{3-[4-(4-ethyl-1,3-thiazol-2-yl)-2-propylphenoxy]propoxy}-1H-indol-1-yl)acetate

HRID 734419Notes

Reaction equation

[NH2:1][C:2]([C:4]1[CH:28]=[CH:27][C:7]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([CH2:22][C:23]([O:25][CH3:26])=[O:24])[CH:17]=[CH:16]3)=[C:6]([CH2:29][CH2:30][CH3:31])[CH:5]=1)=[S:3].Br[CH2:33][C:34](=O)[CH2:35][CH3:36].N1C=CC=CC=1>C(O)C>[CH2:35]([C:34]1[N:1]=[C:2]([C:4]2[CH:28]=[CH:27][C:7]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[N:18]([CH2:22][C:23]([O:25][CH3:26])=[O:24])[CH:17]=[CH:16]4)=[C:6]([CH2:29][CH2:30][CH3:31])[CH:5]=2)[S:3][CH:33]=1)[CH3:36]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of methyl (5-{3-[4-(aminocarbonothioyl)-2-propyl-phenoxy]-propoxy}-1H-indol-1-yl)acetate (Example 52, 500 mg, 1.14 mmol) in ethanol (35 mL), was added 1-bromo-2-butanone (739 mg, 2.27 mmol) and pyridine (0.14 mL, 135 mg, 1.70 mmol). The reaction mixture was stirred for 3 h at 70° C. The solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (0-15% EtOAc in hexane) to give 89 mg (16%) of the title compound. 1H NMR (400 MHz, CDCl3) δ 7.75-7.70 (m, 2H), 7.18-7.12 (m, 2H), 7.05 (d, 1H) 6.95-6.85 (m, 2H), 6.80 (s, 1H), 6.48 (d, 1H), 4.85 (s, 2H), 4.25-4.20 (m, 4H), 3.75 (s, 3H), 2.85 (q, 2H), 2.70-2.60 (m, 2H), 2.40-2.30 (m, 2H), 1.75-1.60 (m, 2H), 1.35 (t, 3H), 0.95 (t, 3H).

Workup

customThe solvent was evaporated under reduced pressure
customthe residue was purified by silica gel chromatography (0-15% EtOAc in hexane)

Sources & evidence

ORD record: ord-6506c01d7f76495390e191f22b3d5cc5
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07592361B2

Reaction notes

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