4-Methylmorpholine → Tert-butyl 4-((4-(3-ethynylphenylamino)quinazolin-6-ylcarbamoyl)methylene)piperidine-1-carboxylate

HRID 2354857Notes

Reaction equation

HRID 2354857 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[CH:14][C:15]([OH:17])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC(C)C)=O.CN1CCOCC1.[C:33]([C:35]1[CH:36]=[C:37]([NH:41][C:42]2[C:51]3[C:46](=[CH:47][CH:48]=[C:49]([NH2:52])[CH:50]=3)[N:45]=[CH:44][N:43]=2)[CH:38]=[CH:39][CH:40]=1)#[CH:34]>N1C=CC=CC=1.C1COCC1>[C:33]([C:35]1[CH:36]=[C:37]([NH:41][C:42]2[C:51]3[C:46](=[CH:47][CH:48]=[C:49]([NH:52][C:15]([CH:14]=[C:11]4[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]4)=[O:17])[CH:50]=3)[N:45]=[CH:44][N:43]=2)[CH:38]=[CH:39][CH:40]=1)#[CH:34]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 10681562(1-Boc-4-piperidinylidene)acetic acidHCID 11492625N4-(3-Ethynylphenyl)quinazoline-4,6-diamine

Product 1

HCID 59382766Tert-butyl 4-((4-(3-ethynylphenylamino)quinazolin-6-ylcarbamoyl)methylene)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

1 g of 2-(1-(tert-butyloxycarbonyl)piperidine-4-ylidene)acetic acid was added to 20 mL of anhydrous THF in a one-neck flask (100 mL). The solution was stirred and cooled on salt-ice bath. Then, 0.6 mL of isobutyl chloroformate and 0.5 mL of N-methylmorpholine were added, and the reaction mixture was let stir for 20 min. 1.046 g of N4-(3-ethynylphenyl)quinazoline-4,6-diamine dissolved in 10 mL of pyridine (dried over molecular sieves) and 0.4 mL of N-methylmorpholine were added to the reaction mixture on an ice bath with stirring. After reaction completion, the solvent was evaporated in vacuo and the remaining residue was partitioned with chloroform and water. The chloroform layer was washed once with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated in vacuo to give a crude product. The crude product was recrystallized from isopropanol. MS (EI) 482 M+.

Workup

  1. temperaturecooled on salt-ice bath
  2. stirringthe reaction mixture was let stir for 20 min
  3. stirringwith stirring
  4. customAfter reaction completion
  5. customthe solvent was evaporated in vacuo
  6. customthe remaining residue was partitioned with chloroform and water
  7. washThe chloroform layer was washed once with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-4957ebdffc8349669d0d2cae4a4eebc5
Source dataset
uspto-grants-2010_07
Patent number
US07754729B2

Reaction notes

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