4-Toluenesulfonyl chloride → 8-bromo-10-tosyl-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole

HRID 1918485Notes

Reaction equation

HRID 1918485 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:17][N:16]4[CH:12]([CH2:13][CH2:14][CH2:15]4)[CH2:11][C:7]=3[NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[S:20](Cl)([C:23]1[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=1)(=[O:22])=[O:21]>C1COCC1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:17][N:16]4[CH:12]([CH2:13][CH2:14][CH2:15]4)[CH2:11][C:7]=3[N:8]2[S:20]([C:23]2[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 580923028-bromo-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole

Product 1

HCID 666033078-bromo-10-tosyl-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indoleYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 8-Bromo-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole (150 mg, 0.52 mmol) in THF (3 mL) was treated sequentially with NaH (31 mg, 0.77 mmol) and TsCl (0.12 g, 0.61 mmol). The reaction mixture was stirred at room temperature under argon overnight. After the mixture was concentrated, the residue was purified by flash column chromatography (silica gel, 5% CH3OH in CH2Cl2) to give 8-bromo-10-tosyl-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole (0.11 g, 48%) as a yellow solid. 8-bromo-10-tosyl-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole (0.11 g, 0.22 mmol) was reacted according to the procedure of Example 2 (step b) to give a yellow solid in 40% (50 mg). The yellow solid was dissolved in CH2Cl2, and NaOH (177 mg, 4.43 mmol) was added. The reaction mixture was stirred at room temperature under argon for 3 h. After the mixture was concentrated, the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give a white solid (30 mg, 83%). The white solid was dissolved in CH3OH (1 mL) and was treated with 2 N HCl in Et2O (1 mL). The resulting solid was isolated by filtration and dried under vacuum to give the title compound (30 mg, 92%) as an off-white powder: mp 270-273° C.; 1H NMR (500 MHz, CD3OD) δ 7.61 (d, J=8.0 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.47-7.31 (m, 6H), 7.04 (dd, J=8.5, 2.0 Hz, 1H), 6.36-6.34 (m, 1H), 6.16 (d, J=2.5 Hz, 1H), 5.20 (s, 2H), 4.89 (d, J=14.0 Hz, 1H), 4.36 (d, J=14.0 Hz, 1H), 3.90-3.85 (m, 2H), 3.49-3.36 (m, 2H), 3.10 (dd, J=15.5, 11.0 Hz, 1H), 2.60-2.55 (m, 1H), 2.36-2.21 (m, 2H), 1.96-1.92 (m, 1H); ESI MS m/z 412 [M+H]+; HPLC (Method A)>99% (AUC), tR=12.7 min.

Workup

  1. concentrationAfter the mixture was concentrated
  2. customthe residue was purified by flash column chromatography (silica gel, 5% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-b5f1b29e39014adcb5d3e42e8fd98d44
Source dataset
uspto-grants-2013_12
Patent number
US08618299B2

Reaction notes

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