(4-Butyl-2-chloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)pyridin-4-ylmethanol.TFA → (4-Butyl-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)pyridin-4-ylmethanol.TFA

HRID 627551Notes

Reaction equation

[CH2:1]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([C:23]3[N:27]([CH3:28])[CH:26]=[N:25][CH:24]=3)([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[OH:16])[CH:13]=2)[N:8]=[C:7](Cl)[C:6]=1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:2][CH2:3][CH3:4].[C:36]([OH:42])([C:38]([F:41])([F:40])[F:39])=[O:37].O(C(C)C)[Na]>CC(O)C>[CH2:1]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([C:23]3[N:27]([CH3:28])[CH:26]=[N:25][CH:24]=3)([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[OH:16])[CH:13]=2)[N:8]=[CH:7][C:6]=1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:2][CH2:3][CH3:4].[C:36]([OH:42])([C:38]([F:41])([F:40])[F:39])=[O:37]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of (4-butyl-2-chloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)pyridin-4-ylmethanol•TFA (16 mg, 0.023 mmol, Example 78) and NaOiPr (19 mg, 0.23 mmol) in iPrOH (0.4 mL) was heated in a sealed tube at 80° C. for 17 hours, and more NaOiPr (7 mg, 0.085 mmol) was added. The mixture was heated for 64 hours and purified by reverse phase HPLC (water/acetonitrile/0.1% TFA) to provide the title compound. 1H NMR (400 MHz, MeOH-d4) δ 9.08 (s, 1H), 8.90 (s, 1H), 8.77 (d, J=6.57 Hz, 3H), 8.29 (d, J=2.02 Hz, 1H), 8.24 (d, J=8.59 Hz, 1H), 8.03 (dd, J=2.02, 9.09 Hz, 1H), 7.83 (d, J=6.57 Hz, 2H), 7.53-7.58 (m, 2H), 7.43 (d, J=6.06 Hz, 2H), 7.18 (s, 1H), 3.72 (s, 3H), 3.06-3.12 (m, 2H), 1.45-1.55 (m, 2H), 1.19-1.28 (m, 2H), 0.78 (t, J=7.33 Hz, 3H); MS m/e 449.2 [M+H]+.

Workup

temperatureThe mixture was heated for 64 hours
custompurified by reverse phase HPLC (water/acetonitrile/0.1% TFA)

Sources & evidence

ORD record: ord-a349b46c7ed4448f964fcfcf676d9fa0
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309222B2

Reaction notes

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