4-Methylmorpholine → N-{4-[(3-Bromophenyl)amino]-3-cyano-8-dimethylaminomethyl-6-quinolinyl}-2-butynamide

HRID 1934975Notes

Reaction equation

[C:1]([OH:6])(=O)[C:2]#[C:3][CH3:4].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:22][C:23]1[CH:24]=[C:25]2[C:30](=[C:31]([CH2:33][N:34]([CH3:36])[CH3:35])[CH:32]=1)[N:29]=[CH:28][C:27]([C:37]#[N:38])=[C:26]2[NH:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([Br:46])[CH:41]=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.O.C(Cl)Cl.C(OCC)(=O)C.CO.C(N(CC)CC)C>[Br:46][C:42]1[CH:41]=[C:40]([NH:39][C:26]2[C:25]3[C:30](=[C:31]([CH2:33][N:34]([CH3:36])[CH3:35])[CH:32]=[C:23]([NH:22][C:1](=[O:6])[C:2]#[C:3][CH3:4])[CH:24]=3)[N:29]=[CH:28][C:27]=2[C:37]#[N:38])[CH:45]=[CH:44][CH:43]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a stirred mixture of 2-butynoic acid (0.42 g, 5.0 mmol) and N-methylmorpholine (0.66 ml, 6.0 mmol) in 4.0 ml of THF at 0° C. was added i-butyl chloroformate (0.52 ml, 4.0 mmol) during 10 m. After 10 m a solution of 6-amino-4-[(3-bromophenyl)amino]-8-dimethylaminomethyl-3-quinolinecarbonitrile (0.79 g, 2.0 mmol) in 4.0 ml of THF was added during 60 s. The mixture was warmed to 25° C., stirred for 2 h, and diluted with water. The pH was adjusted to 9-10 with potassium carbonate, and the resulting solid was filtered off, washed with water, stirred with methylene chloride, and filtered. The latter filtrate was concentrated to give a solid which was subjected to chromatography on silica gel with methylene chloride-ethyl acetate-methanol-triethylamine to give an amber solid; mass spectrum (electrospray, m/e) M+H 462, 464.

Workup

filtrationthe resulting solid was filtered off
washwashed with water
stirringstirred with methylene chloride
filtrationfiltered
concentrationThe latter filtrate was concentrated
customto give a solid which
customto give an amber solid

Sources & evidence

ORD record: ord-ec36271e31f647dcb4eb8291cf04cf0d
Source dataset: uspto-grants-2002_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06384051B1

Reaction notes

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