Hydrazine → (4-methoxy-3-(trifluoromethyl)phenyl)(1H-spiro[chromeno[4,3-c]pyrazole-4,4'-piperidine]-1'-yl)methanone

HRID 1908024Notes

Reaction equation

O[CH:2]=[C:3]1[C:12]2([CH2:17][CH2:16][N:15]([C:18](=[O:31])[C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([C:27]([F:30])([F:29])[F:28])[CH:20]=3)[CH2:14][CH2:13]2)[O:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]1=O.[NH2:33][NH2:34]>C(O)C>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19]([C:18]([N:15]2[CH2:14][CH2:13][C:12]3([C:3]4[CH:2]=[N:34][NH:33][C:4]=4[C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=4[O:11]3)[CH2:17][CH2:16]2)=[O:31])=[CH:20][C:21]=1[C:27]([F:28])([F:29])[F:30]

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of 3-(hydroxymethylene)-1′-[4-methoxy-3-(trifluoromethyl)-benzoyl]spiro[chromane-2,4′-piperidine]-4-one (54 mg, 0.12 mmol) and hydrazine (3.8 μL, 0.12 mmol) in ethanol (1.7 mL) was allowed to stir for 1 h at 25° C., then for 2.5 h at 50° C. The mixture was cooled and then concentrated in vacuo. The residue was taken up in DMF and was purified by reverse phase HPLC to give (4-methoxy-3-(trifluoromethyl)phenyl)(1H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]-1′-yl)methanone. ESI-MS m/z calc. 443.2. found 444.1 (M+1)+; Retention time: 2.40 minutes (4 min run). 1H NMR (400 MHz, CDCl3) δ 9.15-8.90 (m, 1H), 7.73 (s, 1H), 7.67 (d, J=8.3 Hz, 1H), 7.58 (s, 1H), 7.52 (d, J=7.7 Hz, 1H), 7.33-7.18 (m, 1H), 7.04 (dd, J=18.8, 8.3 Hz, 2H), 6.91 (t, J=7.5 Hz, 1H), 6.05-5.60 (m, 1H), 4.50-4.05 (m, 2H), 4.08-3.55 (m, 3H), 3.97 (s, 3H), 2.50-2.32 (m, 2H).

Workup

waitfor 2.5 h at 50° C
temperatureThe mixture was cooled
concentrationconcentrated in vacuo
customwas purified by reverse phase HPLC

Sources & evidence

ORD record: ord-eba0291c4621491e8a04b0a6f6f9cbe5
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598164B2

Reaction notes

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