Hydrochloric Acid → N-(6-chloro-2-(2-cyanopyridin-4-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl)-5-isopropylpyridine-2-sulfonamide

HRID 1871591Notes

Reaction equation

HRID 1871591 reaction equation
[Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH3:16])=[C:6](Cl)[N:5]=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]#[N:25])[CH:19]=2)[N:3]=1.[CH:26]([C:29]1[CH:30]=[CH:31][C:32]([S:35]([NH2:38])(=[O:37])=[O:36])=[N:33][CH:34]=1)([CH3:28])[CH3:27].C(=O)([O-])[O-].[K+].[K+].Cl>CC(C)=O.C1N2CCN(CC2)C1.C(C1C=CC(S(N)(=O)=O)=NC=1)(C)C.O>[Cl:1][C:2]1[N:3]=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]#[N:25])[CH:19]=2)[N:5]=[C:6]([NH:38][S:35]([C:32]2[CH:31]=[CH:30][C:29]([CH:26]([CH3:28])[CH3:27])=[CH:34][N:33]=2)(=[O:37])=[O:36])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH3:16]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 114629344-(4,6-Dichloro-5-(2-methoxyphenoxy)pyrimidin-2-yl)picolinonitrileHCID 181841935-Isopropylpyridine-2-sulfonamide

Product 1

HCID 54403314N-(6-chloro-2-(2-cyanopyridin-4-yl)-5-(2-methoxyphenoxy)pyrimidin-4-yl)-5-isopropylpyridine-2-sulfonamideYield 102.4%

Reagents, catalysts & solvents 4

HCID 9237DabcoCatalyst2×HCID 181841935-Isopropylpyridine-2-sulfonamideCatalystHCID 180AcetoneSolventHCID 962WaterSolvent2×

Conditions

Temperature
40 °C

Procedure

8.95 g (24 mmol) of 4-[4,6-dichloro-5-(2-methoxy-phenoxy)-pyrimidine-2-yl]-pyridine-2-carbonitrile were suspended in 100 ml of acetone. At a temperature of 20° C., 5.04 g (25 mmol) of 5-isopropyl-pyridine-2-sulfonamide, 1 ml of de-ionized water, 10.6 g (77 mmol) of potassium carbonate and 135 mg (1.2 mmol) 1,4-diazobicyclo[2.2.2]octane were added. The mixture was stirred at 40° C. for 20 hr. Thereafter, another 240 mg (1.2 mmol) of 5-isopropyl-pyridine-2-sulfonamide and 80 mg (0.7 mmol) of 1,4-diazobicyclo[2.2.2]octane were added. The reaction mixture was stirred for 24 hr at 40° C. followed by cooling to 20° C. Then 50 ml of de-ionized water and 45 ml of 3 N aqueous hydrochloric acid were added slowly until pH=1. The acetone was removed by distillation and the resulting suspension was stirred at 20° C. for 1.5 hr. The solid was filtered off under suction, washed first with 100 ml of de-ionized water and thereafter with 50 ml of t-butylmethylether. Then the solid was dried at 70° C., 2000 Pa for 20 hr. There were obtained 13.2 g (102% of theory) of 5-isopropyl-pyridin 2-sulfonic acid [6-chloro-2-(2-cyano-pyridine-4-yl)-5-(2-methoxy-phenoxy)-pyrimidine-4-yl]-amide with a HPLC purity of 87.8% (w/w).

Workup

  1. stirringThe reaction mixture was stirred for 24 hr at 40° C.
  2. temperatureby cooling to 20° C
  3. customThe acetone was removed by distillation
  4. stirringthe resulting suspension was stirred at 20° C. for 1.5 hr
  5. filtrationThe solid was filtered off under suction
  6. washwashed first with 100 ml of de-ionized water
  7. customThen the solid was dried at 70° C.
  8. wait2000 Pa for 20 hr

Sources & evidence

ORD record
ord-a5829e667dba467d91941ec1aa1c7743
Source dataset
uspto-grants-2000_08
Patent number
US06103902

Reaction notes

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