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

HRID 2061450ノート

反応式

HRID 2061450 の反応式
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]

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-bf5aa8532199427baac8fba5e91bbe59
出典データセット
uspto-grants-2012_10
特許番号
US08283356B2

反応ノート

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