N-Methyl dicyclohexylamine → 3-Bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-7-carbaldehyde

HRID 913874Notes

Reaction equation

[Br:1][C:2]1[C:10]2[C:5](=[C:6]([CH:12]=[O:13])[CH:7]=[C:8]([Cl:11])[CH:9]=2)[NH:4][N:3]=1.CN(C1CCCCC1)C1CCCCC1.Cl[CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34]>O1CCCC1>[Br:1][C:2]1[C:10]2[C:5](=[C:6]([CH:12]=[O:13])[CH:7]=[C:8]([Cl:11])[CH:9]=2)[N:4]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

3-Bromo-5-chloro-1H-indazole-7-carbaldehyde (1.4 g, 5.4 mmol) and N-methyldicyclohexylamine (1.6 mL, 7.28 mmol) were suspended in tetrahydrofuran (6 mL), cooled to 0° C., and treated with (2-(chloromethoxy)ethyl)trimethylsilane (2.0 mL, 6.74 mmol). The ice bath was removed and stirring continued for 4 h. The reaction was poured into ethyl acetate, washed with water (3×), 1M potassium bisulfate (2×), then brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (10% ethyl acetate/hexanes) gave 1.45 g (69%) as a faint yellow oil. 1H-NMR (CDCl3, 500 MHz) δ 10.28 (s, 1H), 7.97 (d, J=1.83 Hz, 1H), 7.87 (d, J=2.14 Hz, 1H), 6.0(s, 2H), 3.48-3.51 (m, 2H), 0.80-0.83 (m, 2H), 0.10 (s, 9H).

Workup

customThe ice bath was removed
additionThe reaction was poured into ethyl acetate
washwashed with water (3×), 1M potassium bisulfate (2×)
dry with materialbrine (2×), dried over sodium sulfate
concentrationconcentrated
customColumn chromatography on silica gel (10% ethyl acetate/hexanes) gave 1.45 g (69%) as a faint yellow oil

Sources & evidence

ORD record: ord-830184e48cbc4f8299ef55b5f9d73902
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026257B2

Reaction notes

Loading…