1-(3-Nitro-phenyl)vinyltriflate → 6-(1-(3-nitrophenyl)-vinyl)-3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]1H-indazole

HRID 1816809Notes

Reaction equation

HRID 1816809 reaction equation
I[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:19]=[CH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=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.C([Li])CCC.[N+:32]([C:35]1[CH:36]=[C:37]([C:41](OS(C(F)(F)F)(=O)=O)=[CH2:42])[CH:38]=[CH:39][CH:40]=1)([O-:34])=[O:33]>C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N+:32]([C:35]1[CH:36]=[C:37]([C:41]([C:2]2[CH:10]=[C:9]3[C:5]([C:6]([CH:19]=[CH:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)=[N:7][N:8]3[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=2)=[CH2:42])[CH:38]=[CH:39][CH:40]=1)([O-:34])=[O:33]

Participants

7

Reactant 3

HCID 218774861-(3-Nitro-phenyl)vinyltriflateHCID 693701476-iodo-3-styryl-1-[2-(trimethyl-silanyl)ethoxymethyl]-1H-indazoleHCID 178418339Butyllithium

Product 1

HCID 693714336-(1-(3-nitrophenyl)-vinyl)-3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]1H-indazoleYield 52%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of 6-iodo-3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazole, prepared in Example 14, step (i), (330 mg, 0.693 mmol) in THF (3.0 mL) at −78° C. was added n-butyllithium (0.56 mL, 1.5 M, 1.2 equiv). After 20 min, this solution was then added to anhydrous zinc chloride (170 mg) and the mixture was warmed to 23° C. and stirred for 15 min. To this mixture was added 1-(3-nitro-phenyl)vinyltriflate (146 μL, 1.05 equiv) and Pd(PPh3)4 (40 mg, 0.05 equiv). This mixture was stirred for 30 min, was partitioned between ethyl acetate and saturated sodium bicarbonate and the organic layer was separated. The organic material was dried over sodium sulfate, decanted and concentrated under reduced pressure. Purification by silica gel chromatography (1:9 ethyl acetate-hexane) then a second column (1% ethyl acetate/benzene) gave 6-(1-(3-nitrophenyl)vinyl)-3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazole as an oil (180 mg, 52%): FTIR (thin film) 2951, 1616, 1530, 1477, 1448, 1348, 1305, 1248, 1217, 1077, 961, 913, 859 cm−1; 1H NMR (300 MHz, CDCl3) δ 8.26 (t, 1H, J=1.9 Hz), 8.21 (m, 1H), 8.00 (d, 1H, J=8.5 Hz), 7.69 (dt, 1H, J=1.4, 7.8), 7.62-7.28 (m, 9H), 7.19 (dd, 1H, J=1.4, 8.4 Hz), 5.72 (s, 3H), 5.69 (s, 1H), 3.60 (t, 2H, J=8.2 Hz), 0.89 (t, 2H, J=8.2 Hz), −0.05 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 149.9, 149.6, 144.7, 144.5, 142.8, 140.7, 138.6, 135.6, 133.1, 130.7, 130.2, 129.4, 128.0, 124.4, 124.2, 124.1, 123.8, 122.6, 121.2, 118.9, 111.0, 79.2, 68.0, 19.2, 0.0; HRMS (FAB) [M+Na]/z Calc'd 520.2031, found 520.2046.

Workup

  1. stirringThis mixture was stirred for 30 min
  2. customwas partitioned between ethyl acetate and saturated sodium bicarbonate
  3. customthe organic layer was separated
  4. dry with materialThe organic material was dried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated under reduced pressure
  7. customPurification by silica gel chromatography (1:9 ethyl acetate-hexane)

Sources & evidence

ORD record
ord-a73f782462074e9dbd624b898746245a
Source dataset
uspto-grants-2005_04
Patent number
US06884890B2

Reaction notes

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