1,4-Dioxane → HCID 117675756, compound

HRID 1526242Notes

Reaction equation

HRID 1526242 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.O1CCOCC1.CC(C)([O-])C.[K+].Cl[C:27]1[N:28]=[C:29]([NH:39][C:40]2[CH:45]=[CH:44][C:43]([N:46]3[CH2:51][CH2:50][CH:49]([N:52]4[CH2:57][CH2:56][N:55]([CH3:58])[CH2:54][CH2:53]4)[CH2:48][CH2:47]3)=[CH:42][CH:41]=2)[C:30]([C:36]([NH2:38])=[O:37])=[N:31][C:32]=1[CH:33]1[CH2:35][CH2:34]1>O>[C:36]([C:30]1[N:31]=[C:32]([CH:33]2[CH2:35][CH2:34]2)[C:27]([O:1][C@@H:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)=[N:28][C:29]=1[NH:39][C:40]1[CH:45]=[CH:44][C:43]([N:46]2[CH2:47][CH2:48][CH:49]([N:52]3[CH2:57][CH2:56][N:55]([CH3:58])[CH2:54][CH2:53]3)[CH2:50][CH2:51]2)=[CH:42][CH:41]=1)(=[O:37])[NH2:38]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 6544479tert-Butyl (3R)-3-hydroxypyrrolidine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 117667292HCID 117667292, compound

Product 1

HCID 117675756HCID 117675756, compoundYield 75.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (151 mg) and dioxane (4 mL) were added potassium tert-butoxide (91 mg) and 5-chloro-6-cyclopropyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (190 mg), followed by stirring at 100° C. for 16 hours. After leaving to be cooled, water was added thereto, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1) to obtain tert-butyl (3R)-3-{[5-carbamoyl-3-cyclopropyl-6-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]oxy}pyrrolidine-1-carboxylate (189 mg) as a yellow solid.

Workup

  1. customAfter leaving
  2. temperatureto be cooled
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic phase was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1)

Sources & evidence

ORD record
ord-b6d595cd66944e4592ef434b434b7012
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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