Pyrazolidine dihydrochloride → 3-(2-methylsulfanyl-pyrimidin-4-yl)-2-o-tolyloxy-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

HRID 1455240Notes

Reaction equation

Cl.Cl.[NH:3]1[CH2:7][CH2:6][CH2:5][NH:4]1.CO[C:10](=[O:30])[CH:11]([O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:29])[C:12]([C:14]1[CH:19]=[CH:18][N:17]=[C:16]([S:20][CH3:21])[N:15]=1)=O>N1C=CC=CC=1>[CH3:21][S:20][C:16]1[N:15]=[C:14]([C:12]2[N:4]3[CH2:5][CH2:6][CH2:7][N:3]3[C:10](=[O:30])[C:11]=2[O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH3:29])[CH:19]=[CH:18][N:17]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of pyrazolidine-bishydrochloride (1.7 g, 11.6 mmol) in pyridine (30 mL) was added 3-(2-Methylsulfanyl-pyrimidin-4-yl)-3-oxo-2-ortho-tolyloxy-propionic acid methyl ester, 1, (2.0 g, 5.78 mmol). The reaction mixture is heated to 110° C. for 18 h. The solvent is removed in vacuo and the resulting residue is purified by silica gel chromatography (10% MeOH/EtOAc, followed by 20% MeOH/EtOAc) to afford 220 mg (10%) of the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.56 (d, J=5.4 Hz, 1H), 7.57 (d, J=5.4 Hz, 1H), 7.23 (d, J=7.5 Hz, 1H), 7.10 (dd, J=7.5, 7.5 Hz, 1H), 6.96 (dd, J=7.5, 7.5 Hz, 1H), 6.82 (d, J=7.5 Hz, 1H), 4.22 (t, J=6.6 Hz, 2H), 4.05 (t, J=6.9 Hz, 2H), 2.72 (dddd, J=6.9, 6.9, 6.9, 6.9 Hz, 2H), 2.62 (s, 3H), 2.48 (s, 3H); ESI+ MS: m/z (rel intensity) 355.0 (100, M++H).

Workup

customThe solvent is removed in vacuo
customthe resulting residue is purified by silica gel chromatography (10% MeOH/EtOAc, followed by 20% MeOH/EtOAc)

Sources & evidence

ORD record: ord-8588082e15bb4c4499dfae499d461209
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07482356B2

Reaction notes

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