p-Toluenesulfonic acid → HCID 11733337, compound

HRID 1609390Notes

Reaction equation

HRID 1609390 reaction equation
[C:1]([O:4][CH2:5][C@H:6]1[CH2:18][CH2:17][N:9]2[C:10]3[C:15]([CH:16]=[C:8]2[CH2:7]1)=[CH:14][CH:13]=[CH:12][CH:11]=3)(=[O:3])[CH3:2].[C:19](Cl)(=O)[C:20](Cl)=[O:21].Cl.[CH3:26][N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]([CH2:36][C:37](=[NH:42])[O:38]C(C)C)=[CH:28]1.C(N(CC)CC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl.C1(C)C=CC=CC=1.C(OCC)C>[C:1]([O:4][CH2:5][C@H:6]1[CH2:18][CH2:17][N:9]2[C:10]3[C:15]([C:16]([C:19]4[C:20](=[O:21])[NH:38][C:37](=[O:42])[C:36]=4[C:29]4[C:30]5[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=5)[N:27]([CH3:26])[CH:28]=4)=[C:8]2[CH2:7]1)=[CH:14][CH:13]=[CH:12][CH:11]=3)(=[O:3])[CH3:2]

Participants

9

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 10399532HCID 10399532, compoundHCID 22907276Isopropyl 1-methyl-3-indoleacetimidate hydrochloride

Product 1

HCID 11733337HCID 11733337, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A stirred solution of 10 g (41 mmol) of (S)-8-(acetoxy-methyl)-6,7,8,9-tetrahydropyrido[1,2-a]indole in 100ml of dichloromethane was treated dropwise at 0° C. with 4.3 ml (49 mmol) of oxalyl chloride. After 5 minutes, the solvent was removed by evaporation under reduced pressure. The residue was suspended in 150 ml of toluene and treated with 9.5 g (41 mmol) of isopropyl 1-methyl-3-indoleacetimidate hydrochloride (prepared as described in Example 1). The stirred suspension was cooled to 0° C. and treated dropwise with 23 ml (166 mmol) of triethylamine. After stirring for 18 hours at room temperature under nitrogen, the thick suspension was partitioned between dichloromethane, toluene and 0.5M hydrochloric acid. The organic extracts were dried over sodium sulfate, filtered and treated with a suspension of 15.6 g (82 mmol) of p-toluene sulfonic acid in 100 ml of toluene. The mixture was stirred at room temperature for 2.5 hours, washed with water, saturated sodium bicarbonate solution and brine, dried over sodium sulfate and evaporated to give a brown solid. Trituration with diethyl ether gave 13.73 g 72% of (S)-3-[8-(acetoxymethyl)-6,7,8,9tetrahydropyrido[1,2-a ]indol- 10-yl ]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione. A sample was crystallized from dichloromethane/methanol to give an orange solid of melting point 238°-241° C.

Workup

  1. customthe solvent was removed by evaporation under reduced pressure
  2. customthe thick suspension was partitioned between dichloromethane, toluene and 0.5M hydrochloric acid
  3. dry with materialThe organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. stirringThe mixture was stirred at room temperature for 2.5 hours
  6. washwashed with water, saturated sodium bicarbonate solution and brine
  7. dry with materialdried over sodium sulfate
  8. customevaporated
  9. customto give a brown solid

Sources & evidence

ORD record
ord-dce0d411c0524e72981215efe2bf32e3
Source dataset
uspto-grants-1995_03
Patent number
US05399712

Reaction notes

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