Hydrochloric Acid → 6-[2-(4-Methyl-3-methylamino-phenylamino)-pyrimidin-4-ylamino]-2,3-dihydro-benzo[1,4]dioxine-5-sulfonic acid amide

HRID 2242055Notes

Reaction equation

HRID 2242055 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][C:12]3[O:13][CH2:14][CH2:15][O:16][C:11]=3[C:10]=2[S:19]([NH2:22])(=[O:21])=[O:20])[CH:5]=[CH:4][N:3]=1.[CH3:23][C:24]1[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][C:25]=1[NH:31][CH3:32].Cl>C(O)(C)C>[CH3:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:18]=[CH:17][C:12]4[O:13][CH2:14][CH2:15][O:16][C:11]=4[C:10]=3[S:19]([NH2:22])(=[O:21])=[O:20])[CH:5]=[CH:4][N:3]=2)=[CH:26][C:25]=1[NH:31][CH3:32]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14647189N1,6-dimethylbenzene-1,3-diamineHCID 866088546-(2-Chloro-pyrimidin-4-ylamino)-2,3-dihydro-benzo[1,4]dioxine-5-sulfonic acid amide

Product 1

HCID 112015686-[2-(4-Methyl-3-methylamino-phenylamino)-pyrimidin-4-ylamino]-2,3-dihydro-benzo[1,4]dioxine-5-sulfonic acid amide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a suspension of 2.9 g (7.2 mmol) 6-(2-chloro-pyrimidin-4-ylamino)-2,3-dihydro-benzo[1,4]dioxine-5-sulfonic acid amide and 2.0 g 4, N3-dimethyl-benzene-1,3-diamine (compound of Example 102f)) in 50 ml isopropanol is added 5 ml conc. HCl and the reaction mixture is heated to reflux for 2 hours. Then the reaction mixture is partitioned between 1 l ethyl acetate and 1 l water. The aqueous layer is adjusted to slightly basic pH by adding NaHCO3. The water layer is extracted a second time with 300 ml ethyl acetate, the combined organic phases are dried with Na2SO4 and evaporated. The crude product is purified by chromatography on silica gel eluting with ethyl acetate to give in the order of elution a mixture of the two starting materials and the title compound. The mixture of starting materials is again subjected to the reaction conditions and workup giving another 1.21 g (37% yield) of desired product.

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureto reflux for 2 hours
  3. customThen the reaction mixture is partitioned between 1 l ethyl acetate and 1 l water
  4. additionby adding NaHCO3
  5. extractionThe water layer is extracted a second time with 300 ml ethyl acetate
  6. dry with materialthe combined organic phases are dried with Na2SO4
  7. customevaporated
  8. customThe crude product is purified by chromatography on silica gel eluting with ethyl acetate
  9. customto give in the order of elution
  10. additiona mixture of the two starting materials

Sources & evidence

ORD record
ord-88dd1583a95141c0ae3cc7854a2f44de
Source dataset
uspto-grants-2010_03
Patent number
US07671063B2

Reaction notes

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