Hydrochloric Acid → 4-Chloro-6-methoxy-7-(3-morpholinopropoxy)cinnoline

HRID 7482

Reaction equation

Cl[CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[Cl:11][C:12]1[C:21]2[C:16](=[CH:17][C:18]([OH:24])=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[N:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl>CN(C=O)C.C(O)(C)C.O.CO>[Cl:11][C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH2:2][CH2:3][CH2:4][N:5]3[CH2:10][CH2:9][O:8][CH2:7][CH2:6]3)=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[N:14][CH:13]=1

Participants

Conditions

Temperature: 80 °C

Procedure

The starting material 4-chloro-6-methoxy-7-(3-morpholinopropoxy)cinnoline hydrochloride was obtained by adding 1-chloro-3-morpholinopropane (190 mg, 0.95 mmol), (prepared as described in U.S. Pat. No. 4,004,007), to a suspension of 4-chloro-7-hydroxy-6-methoxycinnoline (0.2 g, 0.95 mmol), (prepared as described for the starting material in Example 10), in DMF (5 ml) containing potassium carbonate (327 mg, 2.3 mmol) and potassium iodide (15 mg, 0.095 mmol). After heating at 80° C. for 2 hours, potassium carbonate (65 mg, 0.47 mmol) and more 1-chloro-3-morpholinopropane (95 mg, 0.47 mmol) were added. After stirring for 4 hours at 80° C. the reaction mixture was cooled and 7M hydrogen chloride in isopropanol (407 μl) was added. The solution was poured onto a Diaion (trade mark of Mitsubishi) HP20SS column, using water/methanol (100/0 to 0/100 as a gradient) to give 4-chloro-6-methoxy-7-(3-morpholinopropoxy)cinnoline as an hydrochloride salt (175 mg, 44%).

Workup

custom(prepared
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temperaturewas cooled
additionThe solution was poured onto a Diaion (trade mark of Mitsubishi) HP20SS column

Sources & evidence

ORD record: ord-245f2870f5024f29a93ebbc4e31b8a82
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07087602B2

Linked notes

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