4-Aminopyrimidine → 1-(4-bromo-5-chloro-2-methoxyphenyl)-2-oxo-N-(pyrimidin-4-yl)-1,2-dihydroquinoline-6-sulfonamide

HRID 1504432Notes

Reaction equation

HRID 1504432 reaction equation
[Br:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[CH:12]=[CH:11][C:10]2=[O:34])=[C:4]([O:35][CH3:36])[CH:3]=1.[N:37]1[CH:42]=[CH:41][C:40]([NH2:43])=[N:39][CH:38]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([S:19]([NH:43][C:40]4[CH:41]=[CH:42][N:37]=[CH:38][N:39]=4)(=[O:21])=[O:20])=[CH:16][CH:17]=3)[CH:12]=[CH:11][C:10]2=[O:34])=[C:4]([O:35][CH3:36])[CH:3]=1

Participants

5

Reactant 3

HCID 689584-AminopyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 117736887Perfluorophenyl 1-(4-bromo-5-chloro-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate

Product 1

HCID 1177371541-(4-bromo-5-chloro-2-methoxyphenyl)-2-oxo-N-(pyrimidin-4-yl)-1,2-dihydroquinoline-6-sulfonamideYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A flask was charged with perfluorophenyl 1-(4-bromo-5-chloro-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (0.256 g, 0.419 mmol) and pyrimidin-4-amine (0.048 g, 0.503 mmol). A septum was attached and THF (2.096 ml) was added under N2 flow. The mixture was cooled to 0° C. A THF solution of lithium bis(trimethylsilyl)amide (0.880 ml, 0.880 mmol, 1 M) was added dropwise to give a brown solution with a tan precipitate. The solution was maintained at 0° C. for 20 min, and allowed to warm to rt and maintained for 2 h. The reaction mixture was partitioned between 1 N HCl (10 mL) and EtOAc (20 mL), the layers were separated and the aqueous layer was extracted with 1:1 MeOH:EtOAc (1×20 mL). The combined organic layers which were dried (Na2SO4) and concentrated to provide 1-(4-bromo-5-chloro-2-methoxyphenyl)-2-oxo-N-(pyrimidin-4-yl)-1,2-dihydroquinoline-6-sulfonamide (0.219 g, 0.419 mmol), which was of sufficient purity for the subsequent step. m/z (ESI) 521.1 (M+H)+.

Workup

  1. customto give a brown solution with a tan precipitate
  2. temperatureThe solution was maintained at 0° C. for 20 min
  3. temperatureto warm to rt
  4. temperaturemaintained for 2 h
  5. customThe reaction mixture was partitioned between 1 N HCl (10 mL) and EtOAc (20 mL)
  6. customthe layers were separated
  7. extractionthe aqueous layer was extracted with 1:1 MeOH
  8. dry with materialThe combined organic layers which were dried (Na2SO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-be2cc7582b124010b5416ed971322313
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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