4-Methylmorpholine → HCID 11071370, compound

HRID 379159Notes

Reaction equation

HRID 379159 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH2:9][C:10]#[C:11][C:12]([OH:14])=O.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][CH:40]=1)[N:37]=[CH:36][C:35]([C:41]#[N:42])=[C:34]2[NH:43][C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([Br:50])[CH:45]=1.C([O-])(O)=O.[Na+]>C1COCC1.N1C=CC=CC=1>[Br:50][C:46]1[CH:45]=[C:44]([NH:43][C:34]2[C:33]3[C:38](=[CH:39][CH:40]=[C:31]([NH:30][C:12](=[O:14])[C:11]#[C:10][CH2:9][N:5]4[CH2:6][CH2:7][CH2:8][C@H:4]4[CH2:3][O:2][CH3:1])[CH:32]=3)[N:37]=[CH:36][C:35]=2[C:41]#[N:42])[CH:49]=[CH:48][CH:47]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 99677126-Amino-4-(3-bromophenylamino)quinoline-3-carbonitrileHCID 11805660HCID 11805660, compound

Product 1

HCID 11071370HCID 11071370, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To an ice cold solution of 1.46 g (7.40 mmol) of 4-((2S)-2-methoxymethylpyrrolidin-1-yl)but-2-ynoic acid in 85 mL of THF under N2 was added 0.897 g (8.88 mmol) of N-methylmorpholine and 0.811 g (5.92 mmol) of isobutyl chloroformate. After stirring in the cold for 30 min, a solution of 1.00 g (2.96 mmol) of 6-amino-4-[(3-bromophenyl)amino]-quinoline-3-carbonitrile in 8 mL of pyridine was added dropwise. The reaction was slowly warmed to 25° C. over 3 h. The reaction was poured into ice water, satd NaHCO3 was added and the product was extracted with ethyl acetate. After drying and solvent evaporation, the residue was chromatographed on silica gel (10% methanol in ethyl acetate). The yield was 0.560 g of 4-((2S)-2-methoxymethylpyrrolidinyl-1-yl)but-2-ynoic acid[4-(3-bromophenylamino)-3-cyanoquinolin-6-yl]amide as a brown foam: mass spectrum (electrospray, m/e): M+H 518.0, 520.0.

Workup

  1. additionwas added
  2. extractionthe product was extracted with ethyl acetate
  3. customAfter drying
  4. customsolvent evaporation
  5. customthe residue was chromatographed on silica gel (10% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-3c70d855054345b8a973b0d5e97040ce
Source dataset
uspto-grants-2001_10
Patent number
US06297258B1

Reaction notes

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