Dimethyl Sulfate → methyl-(3-nitro-phenyl)-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-amine

HRID 1861074Notes

Reaction equation

HRID 1861074 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]2[CH:19]=[C:18]3[C:14]([C:15]([CH:28]=[CH:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[N:16][N:17]3[CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])=[CH:13][CH:12]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[CH3:36]OS(OC)(=O)=O.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH3:36][N:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)[C:11]1[CH:19]=[C:18]2[C:14]([C:15]([CH:28]=[CH:29][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[N:16][N:17]2[CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:25])[CH3:26])=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 2733832Lithium HexamethyldisilazideHCID 69371523(3-nitro-phenyl)-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-amine

Product 1

HCID 69369925methyl-(3-nitro-phenyl)-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To (3-nitro-phenyl)-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-amine (434 mg, 0.89 mmol) in THF (5 mL) cooled to −5° C. under an atmosphere of argon, was added dimethylsulfate (0.42 mL, 4.5 mmol) followed by LiHMDS (1M in THF) (1.8 mL, 1.8 mmol). After 20 min the reaction was quenched with saturated NH4Cl (aq) (2 mL), then extracted 3×20 mL EtOAc. The pooled organic material was washed with brine (10 mL), dried with Na2SO4, decanted and concentrated under reduced pressure. Purification by silica gel chromatography (eluting with hexane:EtOAc 9:1) gave methyl-(3-nitro-phenyl)-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-amine, as an oil (367 mg, 82%): TLC (Hexane:EtOAc 7:3) Rf sm 0.29, Rf p 0.39 (ethyl acetate: hexane 3:7); FTIR (KBr) 2951, 2894, 1611, 1528, 1485, 1348, 1248, 1077 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.99 (d, 1H, J=8.67 Hz) 7.77 (t, 1H, J=2.25 Hz), 7.72 (dd, 1H, J=0.79, 2.09 Hz), 7.60, (d, 2H, J=7.22 Hz), 7.26-7.54 (m, 7H), 7.19 (dd, 11H, J=0.78, 2.41 Hz) 7.07 (dd, 1H, J=1.85, 8.69 Hz), 5.70 (s, 2H), 3.63 (t, 2H, J=8.10 Hz), 3.48 (s, 3H), 0.92 (t, 2H, J=8.10 Hz), −0.04 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 150.2, 149.6, 147.1, 143.5, 142.5, 137.3, 131.9, 129.8, 129.0, 128.2, 126.8, 123.1, 122.6, 120.2, 120.0, 119.7, 114.4, 111.4, 104.5, 78.0, 66.8, 41.1, 18.0, −1.2; LCMS (ESI) [M+H]/z Calc'd 501, Found 510.

Workup

  1. customAfter 20 min the reaction was quenched with saturated NH4Cl (aq) (2 mL)
  2. extractionextracted 3×20 mL EtOAc
  3. washThe pooled organic material was washed with brine (10 mL)
  4. dry with materialdried with Na2SO4
  5. customdecanted
  6. concentrationconcentrated under reduced pressure
  7. customPurification
  8. washby silica gel chromatography (eluting with hexane:EtOAc 9:1)

Sources & evidence

ORD record
ord-bbf4dda2585b4b569447beb8d81bc6cc
Source dataset
uspto-grants-2003_03
Patent number
US06531491B1

Reaction notes

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