Hydrochloric Acid → 4-((3-Methoxyphenyl)amino)-8-methyl-6-((3-(4-oxopiperidine-1-carbonyl)phenyl)sulfonyl)quinoline-3-carboxamide

HRID 1944945Notes

Reaction equation

HRID 1944945 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:34]([C:37]1[CH:38]=[N:39][C:40]2[C:45]([C:46]=1[NH:47][C:48]1[CH:53]=[CH:52][CH:51]=[C:50]([O:54][CH3:55])[CH:49]=1)=[CH:44][C:43]([S:56]([C:59]1[CH:60]=[C:61]([CH:65]=[CH:66][CH:67]=1)[C:62]([OH:64])=O)(=[O:58])=[O:57])=[CH:42][C:41]=2[CH3:68])(=[O:36])[NH2:35].O1[C:73]2([CH2:78][CH2:77][NH:76][CH2:75][CH2:74]2)[O:72]CC1.Cl>CN(C=O)C.C1COCC1.CCOC(C)=O.O>[CH3:55][O:54][C:50]1[CH:49]=[C:48]([NH:47][C:46]2[C:45]3[C:40](=[C:41]([CH3:68])[CH:42]=[C:43]([S:56]([C:59]4[CH:67]=[CH:66][CH:65]=[C:61]([C:62]([N:76]5[CH2:77][CH2:78][C:73](=[O:72])[CH2:74][CH2:75]5)=[O:64])[CH:60]=4)(=[O:57])=[O:58])[CH:44]=3)[N:39]=[CH:38][C:37]=2[C:34]([NH2:35])=[O:36])[CH:53]=[CH:52][CH:51]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 577632883-[[3-(Aminocarbonyl)-4-[(3-methoxyphenyl)amino]-8-methyl-6-quinolinyl]sulfonyl]benzoic acid

Product 1

HCID 669882054-((3-Methoxyphenyl)amino)-8-methyl-6-((3-(4-oxopiperidine-1-carbonyl)phenyl)sulfonyl)quinoline-3-carboxamideYield 103.3%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

HATU (348 mg, 0.915 mmol) and DIEA (0.319 mL, 1.83 mmol) were added to a stirring solution of 3-[[3-carbamoyl-4-[(3-methoxyphenyl)amino]-8-methylquinolin-6-yl]sulfonyl]benzoic acid (300 mg, 0.61 mmol) in DMF (6 mL) at rt. After 5 min. 1,4-dioxa-8-azaspiro[4.5]decane (0.156 mL, 1.22 mmol) was added and the resulting solution was stirred for an additional 1.5 h. The reaction mixture was poured into H2O (50 mL) and filtered. The filter cake was washed with H2O then dried to give a yellow solid. To the solid dissolved in THF (6 mL) was added 5 N HCl (1.22 mL, 6.1 mmol). The reaction mixture was heated to 50° C. and stirred over night. The resulting mixture was cooled to rt, and diluted with EtOAc (20 mL). The organic layer was washed with said. NaHCO3 (20 mL), H2O (20 mL), brine (20 mL), dried over Na2SO4 (s), then concentrated to give the title compound (361 mg) as a yellow solid. The compound was used with no further purification. ES/MS calcd. for C30H29N4O6S+ 573.2. Found m/z=573.2 (M+H)+.

Workup

  1. filtrationfiltered
  2. washThe filter cake was washed with H2O
  3. customthen dried
  4. customto give a yellow solid
  5. stirringstirred over night
  6. temperatureThe resulting mixture was cooled to rt
  7. washThe organic layer was washed
  8. dry with materialNaHCO3 (20 mL), H2O (20 mL), brine (20 mL), dried over Na2SO4 (s)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-19dcd888516944c7bb9bb02f6bee2a18
Source dataset
uspto-grants-2013_03
Patent number
US08394829B2

Reaction notes

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