Sodium Chloride → HCID 54498568, compound

HRID 1422291Notes

Reaction equation

HRID 1422291 reaction equation
[Cl:1][CH2:2][C@H:3]1[C:7]2=[C:8]3[C:12](=[C:13]([OH:15])[CH:14]=[C:6]2[N:5]([C:24]([C:26]2[NH:27][C:28]4[C:33]([CH:34]=2)=[CH:32][C:31]([NH:35][C:36]([C:38]2[O:39][C:40]5[C:46]([O:47][CH3:48])=[CH:45][CH:44]=[CH:43][C:41]=5[CH:42]=2)=[O:37])=[CH:30][CH:29]=4)=[O:25])[CH2:4]1)[NH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[C:9]3[C:20]([O:22][CH3:23])=[O:21].Cl[C:50](OC1C=CC([N+]([O-])=O)=CC=1)=[O:51].C(N(CC)CC)C.[NH:69]1[CH2:73][CH2:72][CH2:71][C@H:70]1[CH2:74][OH:75].[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C>[Cl:1][CH2:2][C@H:3]1[C:7]2=[C:8]3[C:12](=[C:13]([O:15][C:50]([N:69]4[CH2:73][CH2:72][CH2:71][C@H:70]4[CH2:74][OH:75])=[O:51])[CH:14]=[C:6]2[N:5]([C:24]([C:26]2[NH:27][C:28]4[C:33]([CH:34]=2)=[CH:32][C:31]([NH:35][C:36]([C:38]2[O:39][C:40]5[C:46]([O:47][CH3:48])=[CH:45][CH:44]=[CH:43][C:41]=5[CH:42]=2)=[O:37])=[CH:30][CH:29]=4)=[O:25])[CH2:4]1)[NH:11][C:10]([C:16]([F:19])([F:17])[F:18])=[C:9]3[C:20]([O:22][CH3:23])=[O:21]

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 8471TriethylamineHCID 821294-Nitrophenyl chloroformateHCID 640091L-ProlinolHCID 10842265HCID 10842265, compound

Product 1

HCID 54498568HCID 54498568, compoundYield 70.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl(1S)-chloromethyl-5-hydroxy-3-[5-(7-methoxybenzofuran-2-ylcarbonyl)amino-1H-indol-2-ylcarbonyl]-7-trifluoromethyl-1,2,3,6-tetrahydropyrrolo[3,2-e]indole-8-carboxylate (10.2 mg, 15 μmol) and 4-nitrophenyl chloroformate (7.6 mg, 38 μmol) were dissolved in 1 mL of tetrahydrofuran, and thereto triethylamine (4.2 μL, 30 μmol) was added dropwise with ice cooling. After one hour, (2S)-pyrrolidine-2-methanol (4.4 μL, 45 μmol) was added dropwise. The mixture was stirred for two hours, and stirred further for two hours at room temperature. The reaction mixture was poured into 3 mL of saturated aqueous sodium chloride solution and 3 mL of ethyl acetate for extraction. The extracted matter was dried over anhydrous sodium sulfate, and the solvent was evaporated off. The resulting residue was purified by silica gel column chromatography (hexane:acetone=1:1) to obtain 8.5 mg (70%) of methyl (1S)-chloromethyl-5-{[(2S)-hydroxymethylpyrrolidin-1-ylcarbonyl]oxy}-3-[5-(7-methoxybenzofuran-2-ylcarbonyl)amino-1H-indol-2-ylcarbonyl]-7-trifluoromethyl-1,2,3,6-tetrahydropyrrolo[3,2-e]indole-8-carboxylate.

Workup

  1. stirringstirred further for two hours at room temperature
  2. dry with materialThe extracted matter was dried over anhydrous sodium sulfate
  3. customthe solvent was evaporated off
  4. customThe resulting residue was purified by silica gel column chromatography (hexane:acetone=1:1)

Sources & evidence

ORD record
ord-f02a1bb50db94fa0b50804aa3be7c50c
Source dataset
uspto-grants-2000_06
Patent number
US06080859

Reaction notes

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