Potassium Iodide → 5-benzyloxy-3-{1-tert-butoxycarbonyl-5-[2-(4-tert-butoxycarbonylpiperazin-1-yl)ethoxy]-1H-indol-2-yl}indazole-1-carboxylic acid tert-butyl ester

HRID 1726087Notes

Reaction equation

HRID 1726087 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:14][CH:15]=2)[C:10]([C:25]2[N:26]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C:27]3[C:32]([CH:33]=2)=[CH:31][C:30]([O:34][CH2:35][CH2:36]Cl)=[CH:29][CH:28]=3)=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].C(O[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])(OC(C)(C)C)=O.CN([C:71]1[CH:76]=C[CH:74]=[CH:73][N:72]=1)C.C(#[N:79])C>ClCCl>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:14][CH:15]=2)[C:10]([C:25]2[N:26]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C:27]3[C:32]([CH:33]=2)=[CH:31][C:30]([O:34][CH2:35][CH2:36][N:72]2[CH2:71][CH2:76][N:79]([C:61]([O:63][C:64]([CH3:65])([CH3:66])[CH3:67])=[O:62])[CH2:74][CH2:73]2)=[CH:29][CH:28]=3)=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 6

HCID 4875Potassium IodideHCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 218852-DimethylaminopyridineHCID 90495Di-tert-butyl dicarbonateHCID 575624225-benzyloxy-3-[1-tert-butoxycarbonyl-5-(2-chloro-ethoxy)-1H-indol-2-yl]indazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 575624995-benzyloxy-3-{1-tert-butoxycarbonyl-5-[2-(4-tert-butoxycarbonylpiperazin-1-yl)ethoxy]-1H-indol-2-yl}indazole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of 330 mg of 5-benzyloxy-3-[1-tert-butoxycarbonyl-5-(2-chloro-ethoxy)-1H-indol-2-yl]indazole-1-carboxylic acid tert-butyl ester, 442 mg of potassium carbonate, 133 mg of potassium iodide and 596 mg of N-1-Boc-piperazine in 15 ml of acetonitrile is stirred at 85° C. for 48 hours. After returning to 20° C, the reaction mixture is evaporated under reduced pressure and the residue is then taken up in a mixture of ethyl acetate (15 ml) and of water (15 ml). After separation by settling out and extraction with ethyl acetate (1×15 ml), the organic extracts are combined, dried over magnesium sulfate and then evaporated under reduced pressure. The crude compound thus obtained is purified by chromatography on silica (AIT column, BPSUP 20-40 μm, 25 g silica; eluent cyclohexane: ethyl acetate 1:1 by volume). The fractions containing the expected compound are combined and evaporated under reduced pressure. The compound thus obtained is dissolved in 10 ml of dichloromethane and then treated with 350 mg of di-tert-butyl dicarbonate and 10 mg of dimethylaminopyridine at 20° C. for 3 hours. The reaction mixture is evaporated under reduced pressure to obtain 220 mg of 5-benzyloxy-3-{1-tert-butoxycarbonyl-5-[2-(4-tert-butoxycarbonylpiperazin-1-yl)ethoxy]-1H-indol-2-yl}indazole-1-carboxylic acid tert-butyl ester, which is characterized, and used without purification.

Workup

  1. customAfter returning to 20° C
  2. customthe reaction mixture is evaporated under reduced pressure
  3. additionthe residue is then taken up in a mixture of ethyl acetate (15 ml) and of water (15 ml)
  4. customAfter separation
  5. extractionextraction with ethyl acetate (1×15 ml)
  6. dry with materialdried over magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe crude compound thus obtained
  9. customis purified by chromatography on silica (AIT column, BPSUP 20-40 μm, 25 g silica; eluent cyclohexane: ethyl acetate 1:1 by volume)
  10. additionThe fractions containing the expected compound
  11. customevaporated under reduced pressure
  12. customThe compound thus obtained
  13. customThe reaction mixture is evaporated under reduced pressure

Sources & evidence

ORD record
ord-cf97da2317974b5184ab37e274a83b91
Source dataset
uspto-grants-2009_02
Patent number
US07491710B2

Reaction notes

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