Acetyl chloride → 1-(1-Acetyl-4-piperidyl)-4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazole-3-carbaldehyde

HRID 908481Notes

Reaction equation

C(N(CC)CC)C.Cl.[NH2:9][C:10]1[N:15]=[CH:14][C:13]([C:16]2[C:17]([CH:27]=[O:28])=[N:18][N:19]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[CH:20]=2)=[CH:12][C:11]=1[C:29]1[O:30][C:31]2[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=2[N:33]=1.[C:38](Cl)(=[O:40])[CH3:39]>C(Cl)Cl>[C:38]([N:24]1[CH2:25][CH2:26][CH:21]([N:19]2[CH:20]=[C:16]([C:13]3[CH:14]=[N:15][C:10]([NH2:9])=[C:11]([C:29]4[O:30][C:31]5[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=5[N:33]=4)[CH:12]=3)[C:17]([CH:27]=[O:28])=[N:18]2)[CH2:22][CH2:23]1)(=[O:40])[CH3:39]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of hydrogen chloride in 2-propanol (2047 μl, 8.19 mmol) at 25° C. was added to tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-formyl-pyrazol-1-yl]piperidine-1-carboxylate (200 mg). The resulting mixture was stirred at 25° C. for 2 hours. The solid was filtered and washed with isopropanol to afford 4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-1-(4-piperidyl)pyrazole-3-carbaldehyde hydrochloride (170 mg). A solution of triethylamine (0.171 ml) was added to 4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-1-(4-piperidyl)pyrazole-3-carbaldehyde hydrochloride (174 mg) dissolved in CH2Cl2 (10 ml) at 0° C. The resulting solution was stirred at 0° C. for 10 minutes. Acetyl chloride (0.032 ml) was added to the mixture at 0° C., then the mixture was stirred at 25° C. for 40 minutes. The mixture was adsorbed on silica gel. The crude product was purified by flash chromatography on silica gel eluting with 1 to 4% methanol in dichloromethane. The solvent was evaporated to dryness to afford 1-(1-acetyl-4-piperidyl)-4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazole-3-carbaldehyde (148 mg) as a pale beige foam. NMR Spectrum: (CDCl3): 2.02-2.15 (m, 2H), 2.17 (s, 3H), 2.23-2.38 (m, 2H), 2.78-2.88 (m, 1H), 3.25-3.36 (m, 1H), 3.99-4.10 (m, 1H), 4.43-4.55 (m, 1H), 4.76-4.87 (m, 1H), 6.92 (bs, 2H), 7.34-7.41 (m, 2H), 7.59 (dd, 1H), 7.65 (s, 1H), 7.74 (dd, 1H), 8.42 (d, 1H), 8.64 (d, 1H), 10.09 (s, 1H); Mass spectrum: M+H+ 431;

Workup

stirringthe mixture was stirred at 25° C. for 40 minutes
customThe crude product was purified by flash chromatography on silica gel eluting with 1 to 4% methanol in dichloromethane
customThe solvent was evaporated to dryness

Sources & evidence

ORD record: ord-59c16c41c57744848206fd2dd7ac292c
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08017611B2

Reaction notes

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