p-Toluenesulfonic acid → 5-Cyano-1H-imidazole-2-carboxylic acid [4-(3,6-dihydro-2H-pyran-4-yl)-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide

HRID 1992029Notes

Reaction equation

[CH3:1][C:2]1([CH3:31])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]3(O)[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH:11]=[CH:10][C:9]=2[NH:21][C:22]([C:24]2[NH:25][C:26]([C:29]#[N:30])=[CH:27][N:28]=2)=[O:23])=[CH:4][CH2:3]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[O:17]1[CH2:16][CH:15]=[C:14]([C:12]2[CH:11]=[CH:10][C:9]([NH:21][C:22]([C:24]3[NH:25][C:26]([C:29]#[N:30])=[CH:27][N:28]=3)=[O:23])=[C:8]([C:5]3[CH2:6][CH2:7][C:2]([CH3:31])([CH3:1])[CH2:3][CH:4]=3)[CH:13]=2)[CH2:19][CH2:18]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of 5-cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(4-hydroxy-tetrahydro-pyran-4-yl)-phenyl]-amide (16.0 mg, 38.1 μmol, as prepared in the previous step) in 0.3 mL of toluene was added p-toluenesulfonic acid (14.0 mg, 74.0 mmol) and the mixture heated to 60° C. for 2 h. The solvent was evaporated and the title compound purified by RP-HPLC, eluting with a linear gradient of 40% CH3CN in 0.1% TFA/H2O to 100% CH3CN over 20 min to give 8.0 mg (50%) of a white solid: 1H-NMR (400 MHz, CD3OD) δ 8.23 (d, J=8.6 Hz, 1H), 8.02 (s, 1H), 7.38 (dd, J=8.6, 2.2 Hz, 1H), 7.26 (d, J=2.2 Hz, 1H), 6.20 (m, 1H), 5.78 (m, 1H), 4.32 (m, 2H), 3.94 (t, J=5.5, 5.5 Hz, 2H), 2.53 (m, 2H), 2.34 (m, 2H), 2.10 (m, 2H), 1.62 (t, J=6.3, 6.3 Hz, 2H), 1.12 (s, 6H). Mass spectrum (ESI, m/z) calcd. for C24H26N4O2 403.2 (M+H), found 403.2.

Workup

customThe solvent was evaporated
customthe title compound purified by RP-HPLC
washeluting with a linear gradient of 40% CH3CN in 0.1% TFA/H2O to 100% CH3CN over 20 min

Sources & evidence

ORD record: ord-fad3a85131ee44168ab3ffb67bd9e825
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07645755B2

Reaction notes

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