1-Methyl-1H-pyrazole-4-carbaldehyde

1-Methyl-1H-pyrazole-4-carbaldehyde is a pharmaceutical intermediate used in the synthesis of the CHK1 inhibitor MK-8776.

Using cyclopropyl methyl ketone and dimethoxy-N, N-dimethylmethylamine as starting materials, the target product 1-Methyl-1H-pyrazole-4-carbaldehyde was obtained through aldol condensation, hydrazine condensation cyclization, selective methylation reaction and Vilsmeier-Hack reaction in sequence, with a total yield of up to 48.0%.

[1] Patent: WO2008/144767, 2008, A1. Location in patent: Page/Page column 117
[2] Patent: EP1762568, 2007, A1. Location in patent: Page/Page column 62
[3] Patent: EP1785418, 2007, A1. Location in patent: Page/Page column 78
[4] Patent: WO2008/153870, 2008, A1. Location in patent: Page/Page column 29
[5] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 1, p. 471 - 474