Hydrochloric Acid → 5-Cyano-4-ethylamino-2-{4-[N-(2-hydroxy-3-piperidinopropyl)sulphamoyl]anilino}pyrimidine

HRID 1071939ノート

反応式

HRID 1071939 の反応式
[OH:1][CH:2]([CH2:15][N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[CH2:3][NH:4][S:5]([C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][CH:9]=1)(=[O:7])=[O:6].Cl.CC(O)CC.Cl[C:29]1[N:34]=[C:33]([NH:35][CH2:36][CH3:37])[C:32]([C:38]#[N:39])=[CH:31][N:30]=1>CO>[C:38]([C:32]1[C:33]([NH:35][CH2:36][CH3:37])=[N:34][C:29]([NH:12][C:11]2[CH:10]=[CH:9][C:8]([S:5](=[O:6])(=[O:7])[NH:4][CH2:3][CH:2]([OH:1])[CH2:15][N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:14][CH:13]=2)=[N:30][CH:31]=1)#[N:39]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 6568(+-)-2-ButanolHCID 223905914-[N-(2-Hydroxy-3-piperidinopropyl)sulphamoyl]anilineHCID 223906122-Chloro-5-cyano-4-ethylaminopyrimidine

生成物 1

HCID 223906225-Cyano-4-ethylamino-2-{4-[N-(2-hydroxy-3-piperidinopropyl)sulphamoyl]anilino}pyrimidine収率 10.2%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
50 °C

実験手順

4-[N-(2-Hydroxy-3-piperidinopropyl)sulphamoyl]aniline (Method 118; 200 mg, 0.64 mmol) was dissolved in methanol (4 ml). 1M Ethereal hydrogen chloride (1.28 ml, 1.28 mmol) was added and the mixture gently warmed to give a solution. The volatiles were partially evaporated to give a volume of approx. 1.5 ml. 2-Butanol (5 ml) was added and the cloudy solution warmed to 50° C. 2-Chloro-5-cyano-4-ethylaminopyrimidine (Method 56; 233 mg, 1.28 mmol) was added in portions and the reaction was then heated at 95° C. for 20 hours. The hot supernatant was decanted from the solid residue and the solution allowed to cool. The resulting precipitate was collected by filtration, washed with diethyl ether and suspended in water (approx. 35 ml). The suspension was adjusted to pH>10 with 2M aqueous sodium hydroxide solution and extracted with ethyl acetate (3×15 ml). The extracts were dried, the volatiles evaporated and the residue purified by chromatography on silica eluting with DCM/methanolic ammonia (100:0) increasing in polarity to (85:15). The product was triturated with diethyl ether and collected by filtration to give the title compound (30 mg, 10%). NMR: 1.15 (t, 3H), 1.35 (m, 2H), 1.43 (m, 4H), 2.10-2.35 (m, 6H), 2.68 (m, 1H), 2.83 (m, 1H), 3.48 (quin, 2H), 3.56 (m, 1H), 4.59 (s, 1H) 7.36 (brt, 1H), 7.70 (d, 2H), 7.88 (t, 1H), 7.95 (d, 2H), 8.40 (s, 1H) 10.16 (s, 1H); m/z: 460.

後処理

  1. temperaturethe mixture gently warmed
  2. customto give a solution
  3. customThe volatiles were partially evaporated
  4. customto give a volume of approx. 1.5 ml
  5. temperaturethe reaction was then heated at 95° C. for 20 hours
  6. customThe hot supernatant was decanted from the solid residue
  7. temperatureto cool
  8. filtrationThe resulting precipitate was collected by filtration
  9. washwashed with diethyl ether
  10. extractionextracted with ethyl acetate (3×15 ml)
  11. customThe extracts were dried
  12. customthe volatiles evaporated
  13. customthe residue purified by chromatography on silica eluting with DCM/methanolic ammonia (100:0)
  14. temperatureincreasing in polarity to (85:15)
  15. customThe product was triturated with diethyl ether
  16. filtrationcollected by filtration

出典と根拠

ORDレコード
ord-b7aa3a14804f4d62a92c4bb4a2aeac07
出典データセット
uspto-grants-2005_06
特許番号
US06908920B2

反応ノート

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