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

HRID 1861073Notes

Reaction equation

HRID 1861073 reaction equation
[CH:1]([C:9]1[C:17]2[C:12](=[CH:13][C:14]([NH2:18])=[CH:15][CH:16]=2)[N:11]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[N:10]=1)=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[N+:27]([C:30]1[CH:31]=[C:32](I)[CH:33]=[CH:34][CH:35]=1)([O-:29])=[O:28].C([O-])([O-])=O.[Cs+].[Cs+].C1(C)C=CC=CC=1>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[N+:27]([C:30]1[CH:35]=[C:34]([NH:18][C:14]2[CH:13]=[C:12]3[C:17]([C:9]([CH:1]=[CH:2][C:3]4[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=4)=[N:10][N:11]3[CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:24])([CH3:26])[CH3:25])=[CH:16][CH:15]=2)[CH:33]=[CH:32][CH:31]=1)([O-:29])=[O:28]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 125741-Iodo-3-nitrobenzeneHCID 693709803-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-ylamine

Product 1

HCID 69371523(3-nitro-phenyl)-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-amineYield 74%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To 3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-ylamine (1.1 g, 3 mmol, m-nitro-iodobenzene (0.9 g, 3.6 mmol), BINAP (0.07 g, 0.133 mmol), Pd2(dba)3 (34 mg, 0.0375 mmol) and Cs2CO3 (1.37 g, 4.2 mmol) under an atmosphere of argon was added toluene (6 mL). The resulting heterogeneous mixture was heated to 80° C. After 46 h the reaction was cooled to 23° C. diluted with ethyl acetate (EtOAc) (20 mL) and filtered. Water (5 mL) was added, the phases were separated, and the organic was extracted 2×50 mL EtOAc. The pooled organic material was washed with brine, then dried with Na2SO4, filtered and concentrated under reduced pressure. The crude reaction was purified by silica gel chromatography (eluting with 9:1 hexane:EtOAc) to give (3-nitro-phenyl)-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-amine as a yellow solid (7.65 g, 74%): TLC (Hexane:EtOAc 7:3) Rf sm 0.16, Rf p 0.30 (ethyl acetate:hexane 3:7); FTIR (KBr) 3391, 3059, 2952, 2894, 1614, 1530, 1483, 1346, 1248, 1076, 836, 734 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.86 (s, 1H), 7.83 (s, 1H), 7.65 (dt, 1H, J=2.21, 5.13 Hz), 7.15-7.41 (m, 5H), 6.93 (dd, 1H, J=1.87, 8.67 Hz), 5.56 (s, 2H), 3.51 (t, 2H, J=8.17 Hz), 0.81 (t, 2H, J=7.96 Hz), −0.15 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 149.6, 144.8, 143.5, 142.4, 140.9, 137.3, 131.8, 130.3, 129.0, 128.2, 126.7, 122.8, 122.6, 120.1, 119.3, 116.1, 115.6, 111.4, 98.5, 77.9,66.7, 18.0, −1.2; MS (ESI) [M+H]/z Calc'd 487, found 487. Anal. Calc'd: C, 66.64; H. 6.21; N, 11.51. Found: C, 66.91; H. 6.21; N, 11.44.

Workup

  1. temperatureAfter 46 h the reaction was cooled to 23° C.
  2. filtrationfiltered
  3. additionWater (5 mL) was added
  4. customthe phases were separated
  5. extractionthe organic was extracted 2×50 mL EtOAc
  6. washThe pooled organic material was washed with brine
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude reaction
  11. customwas purified by silica gel chromatography (eluting with 9:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-1566674589fb4ccd8a3310ecf0d72bda
Source dataset
uspto-grants-2003_03
Patent number
US06531491B1

Reaction notes

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