indium(III)bromide → Methyl (2-bromo-5-(2-phenyl-1H-indole-6-carbonyl)thiophen-3-yl)acetate

HRID 1952501Notes

Reaction equation

HRID 1952501 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:12](=[O:28])[C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[C:15]([NH2:27])[CH:14]=2)=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH3:11])=[O:9].[Br-].[Br-].[Br-].[In+3]>C1(C)C=CC=CC=1>[Br:1][C:2]1[S:3][C:4]([C:12]([C:13]2[CH:14]=[C:15]3[C:16]([CH:19]=[C:20]([C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[NH:27]3)=[CH:17][CH:18]=2)=[O:28])=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH3:11])=[O:9]

Participants

4

Reactant 2

HCID 167051indium(III)bromideHCID 86664844Methyl (2-bromo-5-(3-amino-4-(phenylethynyl)benzoyl)thiophen-3-yl)acetate

Product 1

HCID 86664845Methyl (2-bromo-5-(2-phenyl-1H-indole-6-carbonyl)thiophen-3-yl)acetateYield 85.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 3 (25 mg, 0.05 mmol) in EtOAc (5 mL) was added stannous chloride dihydrate (58 mg, 0.26 mmol). The resulting mixture was refluxed for one hour under N2. The reaction mixture was poured onto ice (5 g), and basified with a saturated NaHCO3 solution to pH 8. The white milky mixture was filtered through a Celite pad to remove tin oxides. The organic layer from the filtrate was dried over MgSO4, filtered, and then concentrated in vacuo. MPLC purification (Hex:EtOAc/4:1) of the crude product gave the desired intermediate methyl (2-bromo-5-(3-amino-4-(phenylethynyl)benzoyl)thiophen-3-yl)acetate as a yellow foam (21 mg, 90%). 1H NMR (400 MHz, CDCl3) δ 7.55 (m, 2H), 7.50 (s, 1H), 7.48 (d, J=1.6 Hz, 1H), 7.38 (m, 3H), 7.17 (m, 2H), 4.40 (brs, 2H), 3.73 (s, 3H), and 3.66 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 186.7, 170.3, 148.1, 143.4, 138.1, 135.9, 135.1, 132.4, 131.8, 129.0, 128.7, 122.9, 122.8, 118.8, 114.5, 112.3, 97.6, 85.3, 52.6, and 35.0; HRMS-ESI calcd C22H16BrNO3S [M+Na] 475.9926. found 475.9923. To a 250 mL flask containing freshly distilled toluene (50 mL) was added methyl (2-bromo-5-(3-amino-4-(phenylethynyl)benzoyl)thiophen-3-yl)acetate (2.93 g, 6.45 mmol) and indium tribromide (1.14 g, 3.22 mmol) under N2. The resulting mixture was refluxed for one hour. The solvent was removed in vacuo. MPLC purification (Hex:EtOAc/4:1) of the crude product gave 4 as a yellow solid (2.50 g, 85%). 1H NMR (400 MHz, CDCl3) δ 9.38 (brs, 1H), 7.98 (s, 1H), 7.69 (d, J=7.8 Hz, 2H), 7.58 (m, 2H), 7.47 (s, 1H), 7.40 (t, J=7.5 Hz, 2H), 7.30 (m, 1H), 6.80 (s, 1H), 3.65 (s, 3H), and 3.59 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 187.4, 170.5, 144.2, 142.3, 136.5, 135.7, 134.9, 133.3, 131.8, 130.9, 129.4, 128.8, 125.9, 121.9, 120.4, 113.5, 100.3, 52.6, and 35.2.

Workup

  1. temperatureThe resulting mixture was refluxed for one hour
  2. customThe solvent was removed in vacuo
  3. customMPLC purification (Hex:EtOAc/4:1) of the crude product

Sources & evidence

ORD record
ord-a45d24271771449ea60ff9e75e8a313d
Source dataset
uspto-grants-2013_03
Patent number
US08404728B2

Reaction notes

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