Ammonia → 4-[3-(2-Chloro-ethyl)-cinnolin-7-yl]-benzonitrile

HRID 273248Notes

Reaction equation

Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](Cl)=[C:7]([CH2:12][CH2:13][Cl:14])[N:8]=[N:9]2)=[CH:4][CH:3]=1.[C:16]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)#[N:17].C([O-])([O-])=O.[Na+].[Na+].N>C(O)(C)C.C1(C)C=CC=CC=1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:14][CH2:13][CH2:12][C:7]1[N:8]=[N:9][C:10]2[C:5]([CH:6]=1)=[CH:4][CH:3]=[C:2]([C:21]1[CH:22]=[CH:23][C:18]([C:16]#[N:17])=[CH:19][CH:20]=1)[CH:11]=2

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of the product from Example 169C (0.095 g, 0.312 mmol), 4-cyanophenylboronic acid (0.046 g, 0.343 mmol), Pd(PPh3)2Cl2 (0.011 g, 0.016 mmol), and 1 M Na2CO3 (0.778 mL, 0.778 mmol) in de-gassed isopropanol/toluene (5 mL, 1:1) was heated to 90° C. under a dry nitrogen atmosphere for 24 hours. After cooling, the reaction mixture was diluted with 20 mL water, extracted twice with 25 mL dichloromethane, and concentrated under reduced pressure. The crude material was purified by column chromatography (1000% dichloromethane to 99:1 dichloromethane/methanol) to afford the product in 50% yield as a brown-orange solid. 1H NMR (CDCl3, 300 MHz) δ 8.76 (d, J=3 Hz, 1H), 8.02 (dd, J=3, 9 Hz, 1H), 7.96 (d, J=9 Hz, 1H), 7.87 (q, J=9 Hz, 4H), 7.80 (s, 1H), 4.14 (t, J=6 Hz, 2H), 3.69 (t, J=6 Hz, 2H). MS (DCl—NH3) [M−Cl]+ at 258, [M+H]+ at 294.

Workup

temperatureAfter cooling
extractionextracted twice with 25 mL dichloromethane
concentrationconcentrated under reduced pressure
customThe crude material was purified by column chromatography (1000% dichloromethane to 99:1 dichloromethane/methanol)
customto afford the product in 50% yield as a brown-orange solid

Sources & evidence

ORD record: ord-b7f11058898841cd9eae48c1291f3136
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07456196B2

Reaction notes

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