4-Methylmorpholine → HCID 22466576, compound

HRID 612105Notes

Reaction equation

HRID 612105 reaction equation
[N:1]1([CH2:7][C:8]#[C:9][C:10]([OH:12])=O)[CH2:6][CH2:5][CH2:4][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][CH:45]=[C:44]([Br:48])[CH:43]=1>C1COCC1.CN(C=O)C.O>[Br:48][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:10](=[O:12])[C:9]#[C:8][CH2:7][N:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)[CH:30]=3)[N:35]=[CH:34][C:33]=2[C:39]#[N:40])[CH:47]=[CH:46][CH:45]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 578964HCID 578964, compoundHCID 99677126-Amino-4-(3-bromophenylamino)quinoline-3-carbonitrile

Product 1

HCID 22466576HCID 22466576, compoundYield 8.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Partially dissolved 1.23 g (7.37 mmol) 4-piperidino-2-butynoic acid in 40 ml THF and chilled to 0° C. under N2. Added 973 μl (8.4 mmol) N-methylmorpholine and 768 μl (5.9 mmol) isobutyl chloroformate. Stirred 10 minutes and added a solution of 1.00 g (2.95 mmol) 6-amino-4-[(3-bromophenyl)amino]-3-quinolinecarbonitrile in 2 ml DMF and 10 ml THF. Removed ice bath at 15 minutes and at 5 hours added 2.95 mmol more of mixed anhydride (0.493 g acid, 487 μl NMM, and 384 μl isobutyl chloroformate), stirred overnight at 25° C. Stripped solvent, slurried residue with water, and collected solids. Boiled in ethyl acetate and collected. Dissolved in 20% methanol/chloroform and coated 5 g of silica gel. Flash chromatographed with 20% methanol/ethyl acetate, stripped solvent of desired fractions and dried in vacuo, giving 122 mg of brown solid: mass spectrum (electrospray m/e): M+H=488.0, 489.9.

Workup

  1. waitRemoved ice bath at 15 minutes
  2. stirringstirred overnight at 25° C
  3. customcollected solids
  4. customcollected
  5. dissolutionDissolved in 20% methanol/chloroform
  6. customFlash chromatographed with 20% methanol/ethyl acetate
  7. customdried in vacuo

Sources & evidence

ORD record
ord-ef85076cfe5c419fa7745e0276688c5d
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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