Hydrochloric Acid → 4-Tert-butyl-n-(6-chloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamide

HRID 589560Notes

Reaction equation

HRID 589560 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH2:14])(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[C:21]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[O:29][CH3:30])=[C:20](Cl)[N:19]=[C:18]([C:32]2[N:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[N:17]=1.C(=O)([O-])[O-].[K+].[K+].Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(C(C)=O)C(C)C.O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:20]2[C:21]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[O:29][CH3:30])=[C:16]([Cl:15])[N:17]=[C:18]([C:32]3[N:37]=[CH:36][CH:35]=[CH:34][N:33]=3)[N:19]=2)(=[O:12])=[O:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2228724-tert-ButylbenzenesulfonamideHCID 105457064,6-Dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine

Product 1

HCID 111351604-Tert-butyl-n-(6-chloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamideYield 92%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 7909Methyl Isobutyl KetoneSolvent

Conditions

Temperature
50 °C

Procedure

44 g (0.21 moles) of 4-tert-butyl-benzenesulfonamide, 72 g (0.21 moles) of 4,6-dichloro-5-(2-methoxy-phenoxy)-[2,2′]bipyrimidine and 0.7 g of tetrabutylammonium bromide are added to a suspension of 35 g (0.25 moles) of potassium carbonate in 720 ml of methyl isobutyl ketone (MIBK), kept in an inert atmosphere (nitrogen). Once the addition is complete, the suspension is heated to reflux, operating so as to azeotropically remove the water that forms during the reaction. The reaction is kept at reflux for 5 hours. Once the reaction is complete, the suspension is cooled to 50° C. and diluted with 0.2 liters of water. Hydrochloric acid 35% is then added until obtaining a pH between 2.0 and 3.0. The suspension is cooled to 5° C./10° C. and the product is left to crystallise for 10 hours. The suspension is filtered and 120 g in wet form of the title compound are obtained equal to 100 g in dry form (0.19 moles) (yield 92%; purity 99.6% HPLC).

Workup

  1. additionOnce the addition
  2. temperaturethe suspension is heated
  3. temperatureto reflux
  4. customto azeotropically remove the water that
  5. customforms during the reaction
  6. temperatureat reflux for 5 hours
  7. customuntil obtaining a pH between 2.0 and 3.0
  8. temperatureThe suspension is cooled to 5° C./10° C.
  9. waitthe product is left
  10. customto crystallise for 10 hours
  11. filtrationThe suspension is filtered

Sources & evidence

ORD record
ord-50ea41929d4544e3bb6e10673cc97654
Source dataset
uspto-grants-2016_01
Patent number
US09233936B2

Reaction notes

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