1,4-Dioxane hydrochloride → 1-(4-(3-(2-(4-Aminocyclohex-1-enyl)ethynyl)pyridin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea, dihydrochloride salt

HRID 2374003Notes

Reaction equation

[F:1][C:2]1[CH:30]=[C:29]([NH:31][C:32]([NH:34][C:35](=[O:44])[CH2:36][C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=2)=[O:33])[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]#[C:12][C:13]1[CH2:18][CH2:17][CH:16]([NH:19]C(=O)OC(C)(C)C)[CH2:15][CH:14]=1.[ClH:45].O1CCOCC1>O1CCOCC1>[ClH:45].[ClH:45].[NH2:19][CH:16]1[CH2:17][CH2:18][C:13]([C:12]#[C:11][C:6]2[CH:7]=[N:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]2[CH:27]=[CH:28][C:29]([NH:31][C:32]([NH:34][C:35](=[O:44])[CH2:36][C:37]3[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=3)=[O:33])=[CH:30][C:2]=2[F:1])=[CH:14][CH2:15]1

Participants

Conditions

Temperature: -5 °C

Procedure

A solution of tert-butyl 4-(2-(4-(2-fluoro-4-(3-(2-(4-fluorophenyl)acetyl)ureido)phenoxy)pyridin-3-yl)ethynyl)cyclohex-3-enylcarbamate (40 mg, 0.066 mol) in anhydrous 1,4-dioxane (2 mL) was cooled to −10° C. and treated with 4 M HCl/1,4-dioxane (4 mL). The mixture was stirred at −5° C. for 2.5 h then at rt for 1 h. The mixture was concentrated under vacuum without any heating to give the title compound (32 mg, 84%) as a yellow solid. 1H NMR (DMSO-d6) δ 11.05 (s, 1H), 10.61 (s, 1H), 8.69 (s, 1H), 8.44 (d, 1H, J=6.1 Hz), 8.06 (d, 1H, J=2.0 Hz), 7.80 (dd, 1H, J=12.7, 2.0 Hz), 7.46-7.38 (m, 1H), 7.35 (dd, 1H, J=8.6, 5.6 Hz), 7.19-7.13 (m, 1H), 6.82 (d, 1H, J=5.6 Hz), 6.17 (s, 1H), 3.74 (s, 2H), 3.73-3.62 (m, 2H), 3.62-3.54 (m, 1H), 3.34-3.22 (m, 1H), 2.31 (s, 1H), 1.99-1.96 (m, 1H), 1.71-1.66 (m, 1H); MS(ESI+): m/z 503.12 (M+H)+.

Workup

waitat rt for 1 h
concentrationThe mixture was concentrated under vacuum without any heating

Sources & evidence

ORD record: ord-68386f00fc744e4db31022d1115357ef
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07459562B2

Reaction notes

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