4-Methylmorpholine → HCID 22466694, compound

HRID 612018Notes

Reaction equation

HRID 612018 reaction equation
ClC(OCC(C)C)=O.CN1CCOCC1.[C:16]([Si:20]([CH3:29])([CH3:28])[O:21][CH2:22][C:23]#[C:24][C:25]([OH:27])=O)([CH3:19])([CH3:18])[CH3:17].[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>O1CCCC1.N1C=CC=CC=1.C(OCC)(=O)C>[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:25](=[O:27])[C:24]#[C:23][CH2:22][O:21][Si:20]([C:16]([CH3:17])([CH3:18])[CH3:19])([CH3:29])[CH3:28])[CH:32]=3)[N:37]=[CH:36][C:35]=2[C:41]#[N:42])[CH:49]=[CH:48][CH:47]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 99677126-Amino-4-(3-bromophenylamino)quinoline-3-carbonitrileHCID 224784454-{[tert-Butyl(dimethyl)silyl]oxy}but-2-ynoic acid

Product 1

HCID 22466694HCID 22466694, compoundYield 35%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Isobutyl chloroformate(0.214 g, 1.57 mmol) and N-methylmorpholine(0.190 g, 1.88 mmol) were added to an ice cold solution of 0.336 g (1.57 mmol) of 4(tert-butyl-dimethyl-silanyloxy)-2-butynoic acid in 15 mL of tetrahydrofuran under N2. After stirring for 30 min, it was transferred to an additional funnel plugged with a glass wool and added dropwise to a solution of 0.4 g (1.18 mmol) of 6-amino-4-[(3-bromophenyl)amino]-3-quinolinecarbonitrile in 3 mL of tetrahydrofuran and 1.5 ml of pyridine. The mixture was stirred at 25° C. for 1 h. The reaction solution was poured into ethyl acetate and washed with saturated sodium bicarbonate and brine. The product was collected and purified by flash column chromatography (60% ethyl acetate in hexane) to give 0.220 g of N-[4-[(3-Bromophenyl)amino]-3-cyano-6-quinolinyl]-4-(tert-butyl-dimethyl-silanyloxy)-2-butynamide as a yellow solid (35%); ESMS m/z 535.1 (M+H+); mp ° C.(dec).

Workup

  1. customit was transferred to an additional funnel
  2. stirringThe mixture was stirred at 25° C. for 1 h
  3. washwashed with saturated sodium bicarbonate and brine
  4. customThe product was collected
  5. custompurified by flash column chromatography (60% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ecb073e83cbd4f8d9b70dec725248564
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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