Isobutyl chloroformate → Tert-butyl 4-(2-(4-(3-chloro-4-(pyridin-2-YL-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-YL-oxy)quinolin-6-YL-amino)-2-oxo ethylidene)piperidine-1-carboxylate

HRID 714585Notes

Reaction equation

HRID 714585 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.CN1[C@@H]2CC3C=CC(OC)=C4O[C@H]5[C@@H](O)C=C[C@@H]2[C@]5(C=34)CC1.[NH2:48][C:49]1[CH:50]=[C:51]2[C:56](=[CH:57][C:58]=1[O:59][CH:60]1[CH2:64][CH2:63][O:62][CH2:61]1)[N:55]=[CH:54][C:53]([C:65]#[N:66])=[C:52]2[NH:67][C:68]1[CH:73]=[CH:72][C:71]([O:74][CH2:75][C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][N:77]=2)=[C:70]([Cl:82])[CH:69]=1>N1C=CC=CC=1.C1COCC1>[Cl:82][C:70]1[CH:69]=[C:68]([NH:67][C:52]2[C:51]3[C:56](=[CH:57][C:58]([O:59][CH:60]4[CH2:64][CH2:63][O:62][CH2:61]4)=[C:49]([NH:48][C:15](=[O:17])[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)[CH:50]=3)[N:55]=[CH:54][C:53]=2[C:65]#[N:66])[CH:73]=[CH:72][C:71]=1[O:74][CH2:75][C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][N:77]=1

Participants

7

Reactant 4

HCID 62365Isobutyl chloroformateHCID 5284371CodeineHCID 10681562(1-Boc-4-piperidinylidene)acetic acidHCID 866945566-Amino-4-(3-chloro-4-(pyridin-2-yl-methoxy)phenylamino)-7-(tetrahydrofuran-3-yl-oxy)quinolin-3-carbonitrile

Product 1

HCID 56592472Tert-butyl 4-(2-(4-(3-chloro-4-(pyridin-2-YL-methoxy)phenylamino)-3-cyano-7-(tetrahydrofuran-3-YL-oxy)quinolin-6-YL-amino)-2-oxo ethylidene)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

To a single-neck reaction flask (100 ml) were added 2-(1-(tert-butyloxycarbonyl)piperidin-4-ylidene)acetic acid (1 g) and anhydrous THF (20 ml). The mixture was stirred to dissolve and cooled to the temperature of −5° C. To the mixture were added isobutyl chloroformate (0.6 ml) and N-methylmorphine (0.5 ml). The resultant mixture was stirred for 20 min. 6-amino-4-(3-chloro-4-(pyridin-2-yl-methoxy) phenylamino)-7-(tetrahydrofuran-3-yl-oxy)quinolin-3-carbonitrile (2 g, 4.1 mmol) was dissolved in anhydrous pyridine (20 ml). The resulting solution was added into the reaction flask in an ice-water bath. After the reaction finished, the solvent was rotary-evaporated to dryness. To the residue were added chloroform and water. The solution was stood for separation. The chloroform layer was wash once with saturated saline solution, dried over anhydrous magnesium sulfate, filtered and rotary-evaporated to dryness to give a crude product. The product was recrystallized with ethanol.

Workup

  1. dissolutionto dissolve
  2. additionThe resulting solution was added into the reaction flask in an ice-water bath
  3. customthe solvent was rotary-evaporated to dryness
  4. additionTo the residue were added chloroform and water
  5. customThe solution was stood for separation
  6. washThe chloroform layer was wash once with saturated saline solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customrotary-evaporated to dryness

Sources & evidence

ORD record
ord-9ac6150d5f034584b2504f1aad9f334c
Source dataset
uspto-grants-2015_11
Patent number
US09187458B2

Reaction notes

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