Triethylamine → 3[8(S)-[1(S)-tert.butoxy formamido-2-methylpropyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-phenyl-3-indolyl)-furan-2,5-dione

HRID 863547Notes

Reaction equation

HRID 863547 reaction equation
[CH:1]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:2]=1[CH:3]=[C:4]1[CH2:13][C@@H:12]([C@@H:14]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:15]([CH3:17])[CH3:16])[CH2:11][CH2:10][N:5]12.[C:26](Cl)(=O)[C:27](Cl)=[O:28].[C:32]1([N:38]2[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40]([CH2:47][C:48]([OH:50])=[O:49])=[CH:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(N(CC)CC)C>C(OCC)C.ClCCl>[C:21]([O:20][C:19]([NH:18][C@H:14]([C@H:12]1[CH2:11][CH2:10][N:5]2[C:6]3[C:2]([C:3]([C:26]4[C:27](=[O:28])[O:49][C:48](=[O:50])[C:47]=4[C:40]4[C:41]5[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=5)[N:38]([C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=5)[CH:39]=4)=[C:4]2[CH2:13]1)=[CH:1][CH:9]=[CH:8][CH:7]=3)[CH:15]([CH3:17])[CH3:16])=[O:25])([CH3:23])([CH3:22])[CH3:24]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 196961141-Phenylindole-3-acetic acidHCID 86752150tert.butyl [1(S)-[6,7,8,9-tetrahydropyrido[1,2-a]indol-8(S)-yl]-2-methylpropyl]carbamate

Product 1

HCID 867521493[8(S)-[1(S)-tert.butoxy formamido-2-methylpropyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-phenyl-3-indolyl)-furan-2,5-dioneYield 29%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent

Procedure

An ice-cooled solution of 3 g (8.77 mmol) of tert.butyl [1(S)-[6,7,8,9-tetrahydropyrido[1,2-a]indol-8(S)-yl]-2-methylpropyl]carbamate, prepared as described in Example 11(iv), in 50 ml of anhydrous diethyl ether was treated dropwise under a nitrogen atmosphere over a period of 5 minutes with a solution of 0.85 ml (9.74 mmol) of oxalyl chloride in 5 ml of anhydrous diethyl ether. After an additional 5 minutes, the solvent was removed under reduced pressure and the residue was dissolved in 50 ml of dry dichloromethane. The solution was added dropwise at 0° C. to a stirred mixture of 2.2 g (8.77 mmol) of 1-phenylindole-3-acetic acid and 3.65 ml (26.3 mmol) of triethylamine in 50 ml of dry dichloromethane. The mixture was stirred for 17 hours and then the solvent was removed under reduced pressure. Purification by flash chromatography on silica gel using ethyl acetate/hexane (1:2) for the elution followed by crystallization from ethyl acetate/hexane gave 1.6 g of 3[8(S)-[1(S)-tert.butoxyformamido-2-methylpropyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-phenyl-3-indolyl)-furan-2,5-dione as an orange coloured solid of melting point 148°-150° C.

Workup

  1. customprepared
  2. customthe solvent was removed under reduced pressure
  3. dissolutionthe residue was dissolved in 50 ml of dry dichloromethane
  4. customthe solvent was removed under reduced pressure
  5. customPurification by flash chromatography on silica gel
  6. washfor the elution
  7. customfollowed by crystallization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-ccf3be1fd2e64d7cb30ea83496928303
Source dataset
uspto-grants-1998_02
Patent number
US05721230

Reaction notes

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