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

HRID 2390422Notes

Reaction equation

HRID 2390422 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

8

Reactant 4

HCID 222AmmoniaHCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 671047587-Bromo-4-chloro-3-(2-chloro-ethyl)-cinnoline

Product 1

HCID 671047734-[3-(2-Chloro-ethyl)-cinnolin-7-yl]-benzonitrileYield 50%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 21881414Toluene isopropyl alcoholSolvent

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 (100% 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 (DCI-NH3) [M-Cl]+ at 258, [M+H]+ at 294.

Workup

  1. temperatureAfter cooling
  2. extractionextracted twice with 25 mL dichloromethane
  3. concentrationconcentrated under reduced pressure
  4. customThe crude material was purified by column chromatography (100% dichloromethane to 99:1 dichloromethane/methanol)
  5. customto afford the product in 50% yield as a brown-orange solid

Sources & evidence

ORD record
ord-b07dd741001d4601803e5ec2765f0ef6
Source dataset
uspto-grants-2012_09
Patent number
US08273767B2

Reaction notes

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