4-Methylmorpholine → HCID 10885120, compound

HRID 1935000Notes

Reaction equation

[N:1]1([CH2:7][C:8](=[CH2:12])[C:9]([OH:11])=O)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[N:35]=[CH:34][C:33]([C:39]#[N:40])=[C:32]2[NH:41][C:42]1[CH:47]=[CH:46][C:45]([F:48])=[C:44]([Cl:49])[CH:43]=1.C(=O)(O)[O-].[Na+]>C1COCC1.N1C=CC=CC=1>[Cl:49][C:44]1[CH:43]=[C:42]([NH:41][C:32]2[C:31]3[C:36](=[CH:37][CH:38]=[C:29]([NH:28][C:9](=[O:11])[C:8]([CH2:7][N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)=[CH2:12])[CH:30]=3)[N:35]=[CH:34][C:33]=2[C:39]#[N:40])[CH:47]=[CH:46][C:45]=1[F:48]

Participants

Conditions

Temperature: 0 °C

Procedure

Partially dissolved 1.37 g (8.00 mmol) 2-morpholin-4-ylmethyl-2-propenoic acid in 50 ml THF and chilled to 0° C. under N2. Added 1.06 ml (9.6 mmol) N-methylmorpholine and 833 μl (6.4 mmol) isobutyl chloroformate. Stirred at 0° C. for 1 hour and added a solution of 1.00 g (3.20 mmol) 6-amino-4-[(3-chloro-4-fluorophenyl)amino]-3-quinolinecarbonitrile in 5 ml pyridine. Stirred overnight at 25° C. Poured onto a mixture of ice and saturated sodium bicarbonate, extracted with ethyl acetate, dried organic layer with brine and sodium sulfate, and stripped solvent to a small volume. Loaded onto a column of silica gel, eluted with 1% methanol/ethyl acetate, stripped solvent from desired fractions and dried under vacuum, giving 139 mg of yellow-orange solid: mass spectrum (electrospray m/e): M+H=465.8, 468.0.

Workup

stirringStirred overnight at 25° C
extractionextracted with ethyl acetate, dried organic layer with brine and sodium sulfate
washeluted with 1% methanol/ethyl acetate
customdried under vacuum

Sources & evidence

ORD record: ord-785b9dc933ad4dd080ea9b82a7a8fcb4
Source dataset: uspto-grants-2002_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06384051B1

Reaction notes

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