Methanol → 3-(1,1-dimethoxy-methyl)-6-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole

HRID 724414Notes

Reaction equation

HRID 724414 reaction equation
[I:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](C=CC3C=CC=CC=3)=[N:7][N:8]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.CO.O=[O+][O-].[CH:32]([O:37][CH3:38])([O:35][CH3:36])OC>C(Cl)Cl>[CH3:38][O:37][CH:32]([C:6]1[C:5]2[C:9](=[CH:10][C:2]([I:1])=[CH:3][CH:4]=2)[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:7]=1)[O:35][CH3:36]

Participants

6

Reactant 4

HCID 887MethanolHCID 9005Trimethyl orthoformateHCID 24823OzoneHCID 693701476-iodo-3-styryl-1-[2-(trimethyl-silanyl)ethoxymethyl]-1H-indazole

Product 1

HCID 218772983-(1,1-dimethoxy-methyl)-6-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazoleYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 6-iodo-3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazole [Example 14, step (i)] (1.28 g, 2.69 mmol) in CH2Cl2 (40 mL)/MeOH (40 mL) was stirred at −78° C. The reaction was treated with ozone until a blue color persisted, and then was purged with argon. Methyl sulfide (4 mL) was added, and the reaction stirred 4 h while warming to r.t. Concentration in vacuo gave a crude mixture of acetal and aldehyde, which was converted completely to the acetal by stirring in trimethyl orthoformate (10 mL) with Amberlyst 15 (wet) acidic ion-exchange resin (0.8 g) for 1 h. The resin was removed by filtration, and the solution was concentrated in vacuo. Purification by silica gel chromatography gave 1.11 g (92%) of 3-(1,1-dimethoxy-methyl)-6-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole as a clear oil. 1H NMR (300 MHz, CDCl3) δ 7.98 (s, 1H), 7.68 (d, 1H, J=8.4 Hz), 7.48 (dd, 1H, J=8.4, 1.2 Hz), 5.77 (s, 1H), 5.69 (s, 2H), 3.53 (t, 2H, J=8.4 Hz), 3.43 (s, 6H), 0.88 (t, 2H, J=8.4 Hz), −0.06 (s, 9H).

Workup

  1. customwas purged with argon
  2. additionMethyl sulfide (4 mL) was added
  3. concentrationConcentration in vacuo
  4. customgave a crude
  5. customThe resin was removed by filtration
  6. concentrationthe solution was concentrated in vacuo
  7. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-c52a731775074e36a431d8c06df0b338
Source dataset
uspto-grants-2006_11
Patent number
US07141587B2

Reaction notes

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