p-Toluenesulfonic acid monohydrate → HCID 73335823, compound

HRID 710658Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:28])[CH2:18][N:19]4[CH:23]=[C:22]([C:24]([NH2:27])=[N:25][OH:26])[CH:21]=[N:20]4)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:29]C1C=CC(S(O)(=O)=O)=CC=1.O>C(OC)(OC)OC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:28])[CH2:18][N:19]4[CH:23]=[C:22]([C:24]5[N:27]=[CH:29][O:26][N:25]=5)[CH:21]=[N:20]4)[C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 1-[2-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-oxo-ethyl]-N′-hydroxy-pyrazole-4-carboxamidine (0.115 g, 0.30 mmol) and p-TsOH.H2O (0.030 g, 0.15 mmol) in HC(OMe)3 (3 mL) was heated at 100° C. for 1.5 hrs. It was then cooled to rt. The mixture was partitioned between IPA/CHCl3 (1:2, 50 mL) and sat. NaHCO3 (30 mL). The organic layer was separated, dried over Na2SO4, concentrated in vacuo and purified by reverse phase HPLC to afford the desired product (0.055 g, 21%). 1H NMR (400 MHz, CDCl3) δ 8.71 (s, 1H), 7.65-8.50 (m, 3H), 7.44 (dd, J=8.4, 4.6 Hz, 2H), 7.17 (dd, J=9.2, 7.6 Hz, 2H), 5.27 (m, 2H), 3.85 (m, 2H), 2.85 (m, 2H), 2.14 (m, 2H); MS: (ES) m/z calculated for C19H16FN7O2 [M+H]+ 394.1, found 394.1.

Workup

temperatureIt was then cooled to rt
customThe mixture was partitioned between IPA/CHCl3 (1:2, 50 mL) and sat. NaHCO3 (30 mL)
customThe organic layer was separated
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-e98a0edfa88640eab26bd9efe87da847
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181241B2

Reaction notes

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