Guanidine Hydrochloride → 2-amino-7-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)-4-methyl-7,8-dihydroquinazolin-5(6H)-one

HRID 1917476Notes

Reaction equation

[C:1]([C:4]1[C:5](=[O:24])[CH2:6][CH:7]([C:11]2[S:12][CH:13]=[CH:14][C:15]=2[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[N:17]=2)[CH2:8][C:9]=1O)(=O)[CH3:2].N1CCCC1.Cl.[NH2:31][C:32]([NH2:34])=[NH:33]>CCO>[NH2:34][C:32]1[N:33]=[C:1]([CH3:2])[C:4]2[C:5](=[O:24])[CH2:6][CH:7]([C:11]3[S:12][CH:13]=[CH:14][C:15]=3[C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[N:17]=3)[CH2:8][C:9]=2[N:31]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a 150 mL pressure vessel was added 2-acetyl-3-hydroxy-5-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)cyclohex-2-enone (30G, 1.72 g, 5.01 mmol, 1.0 eq.), EtOH (50 mL), pyrrolidine (2.13 g, 30.1 mmol, 6.0 eq.), guanidine hydrochloride (1.44 g, 15 mmol, 3.0 eq.). The vessel was sealed and heated overnight at 100° C. LC/MS analysis showed the reaction to be complete whereupon the reaction mixture was concentrated and the residue was taken up in 20% EtOAc/CH2Cl2. An insoluble solid proving not to be product was filtered off The remaining filtrate was purified via column chromatography (20% EtOAc/CH2Cl2 to 70% EtOAc/CH2Cl2) to yield the product 30H as a light gray solid (270 mg, 15%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.55 (s, 3H) 2.76-2.95 (m, 2H) 3.02-3.22 (m, 2H) 3.70 (s, 3H) 4.62-4.77 (m, 1H) 6.72 (d, J=8.34 Hz, 1H) 7.31 (d, J=7.58 Hz, 1H) 7.41-7.54 (m, 4H) 7.75 (t, J=7.83 Hz, 1H). ESI-MS: m/z 367.3 (M+H)+.

Workup

customThe vessel was sealed
customthe reaction
concentrationwas concentrated
filtrationwas filtered off The remaining filtrate
customwas purified via column chromatography (20% EtOAc/CH2Cl2 to 70% EtOAc/CH2Cl2)

Sources & evidence

ORD record: ord-94ced04b38d34a9387294d943b02819b
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618290B2

Reaction notes

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