Phosgene → 5-Isocyanatoisoquinoline

HRID 2092178Notes

Reaction equation

[C:1](Cl)(Cl)=[O:2].[NH2:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][N:10]=[CH:11]2>CN(C)C1C=CN=CC=1.C(Cl)Cl>[N:5]([C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][N:10]=[CH:11]2)=[C:1]=[O:2]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of phosgene (20% in toluene, 5.8 ml, 11 mmol) was added to 50 ml methylene chloride and cooled to 0° C. 4-Dimethylaminopyridine (2.86 g, 23.4 mmol) in 30 ml methylene chloride was added dropwise. A thick white suspension formed. A solution of 5-aminoisoquinoline (1.44 g, 10 mmol) in 30 ml methylene chloride was then added dropwise to this suspension. The reaction was allowed to warm to ambient temperature and stirred overnight. At the end of this time, a solution formed, and the solvent was removed under reduced pressure. The residue was triturated with 50 ml diethyl ether to give an approximately 0.1 M solution of 5-isocyanato-isoquinoline. 32 ml of this solution was added to Example 35E (0.70 g, 3.2 mmol), and the reaction stirred overnight. The precipitate that formed was collected by filtration to give 0.43 g of Example 35F. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.28 (s, 1 H), 8.65 (s, 1 H), 8.54 (d, J=6.10 Hz, 1 H), 8.31-8.37 (m, 1 H), 7.90 (d, J=6.10 Hz, 1 H), 7.76 (d, J=8.14 Hz, 1 H), 7.55-7.66 (m, 2 H), 7.24-7.29 (m, 1 H), 7.13-7.22 (m, 2 H), 5.03 (m, 1 H) 4.38 (m, 1 H) 4.27 (m, 3.22 Hz, 1 H) 2.14-2.26 (m, 1 H) 2.08 (m, 1 H). MS (ESI) m/e 388 (M+H)+.

Workup

customA thick white suspension formed
temperatureto warm to ambient temperature
customAt the end of this time, a solution formed
customthe solvent was removed under reduced pressure
customThe residue was triturated with 50 ml diethyl ether

Sources & evidence

ORD record: ord-d426aaf6b1194c97b73201cc49d3a5b4
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08440691B2

Reaction notes

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