Hydrazine hydrate (1:1) → 1-(cyclopropylmethyl)-3-(4-methyl-5-(5-methyl-1H-pyrazol-3-yl)thiazol-2-yl)imidazolidin-2-one

HRID 1882444Notes

Reaction equation

[C:1]([C:4]1[S:8][C:7]([N:9]2[CH2:13][CH2:12][N:11]([CH2:14][CH:15]3[CH2:17][CH2:16]3)[C:10]2=[O:18])=[N:6][C:5]=1[CH3:19])(=O)[CH3:2].CO[C:22](OC)([N:24](C)C)[CH3:23].O.[NH2:30]N>CN(C)C(=O)C>[CH:15]1([CH2:14][N:11]2[CH2:12][CH2:13][N:9]([C:7]3[S:8][C:4]([C:1]4[CH:2]=[C:22]([CH3:23])[NH:24][N:30]=4)=[C:5]([CH3:19])[N:6]=3)[C:10]2=[O:18])[CH2:17][CH2:16]1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 1-(5-acetyl-4-methylthiazol-2-yl)-3-(cyclopropylmethyl)-imidazolidin-2-one (0.28 g, 1.00 mmol) in N,N-dimethylacetamide (10 mL) was added N,N-dimethylacetamide dimethyl acetal (1.4 mL, 8.60 mmol). The reaction mixture was heated for 20 hours at 110° C., followed by the addition of hydrazine monohydrate (2.0 mL, 41.12 mmol). The reaction mixture was heated for another 10 minutes at 110° C. and concentrated in vacuo. The residue was washed with water and triturated with ethyl acetate and the title compound was obtained as a white solid in 71% yield (0.23 g): mp 231-233° C. (ethyl acetate); 1H NMR (300 MHz, DMSO-d6) δ 12.5 (s, 1H), 6.15 (s, 1H), 3.98-3.92 (m, 2H), 3.62-3.57 (m, 2H), 3.05 (d, J=7.2 Hz, 2H), 2.33 (s, 3H), 2.21 (s, 3H), 0.95-0.84 (m, 1H), 0.49-0.43 (m, 2H), 0.21-0.17 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 155.8, 155.5, 144.4, 142.1, 139.9, 129.0, 102.5, 48.2, 42.5, 42.3, 16.9, 10.8, 9.3, 3.6; MS (ES+) m/z 318.2 (M+1).

Workup

temperatureThe reaction mixture was heated for another 10 minutes at 110° C.
concentrationconcentrated in vacuo
washThe residue was washed with water
customtriturated with ethyl acetate

Sources & evidence

ORD record: ord-19120a01f7c7490da29a149522d80dfa
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318949B2

Reaction notes

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