4-Methylmorpholine → HCID 11071370, compound

HRID 548462Notes

Reaction equation

HRID 548462 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-e47994c7cbe546ba8d802acd847432a8
Source dataset
uspto-grants-2011_05
Patent number
USRE042376E1

Reaction notes

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