Hydrochloric Acid → Ethyl 6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridine-3-carboxylate

HRID 860832

反応式

HRID 860832 の反応式
[CH2:1]([O:3][C:4](=[O:17])[C:5](Cl)=[N:6][NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1)[CH3:2].[I:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH2:30][CH2:29][CH:28]=[C:27](N3CCOCC3)[C:26]2=[O:37])=[CH:21][CH:20]=1.C(N(CC)CC)C.Cl>CCOC(C)=O.O>[CH2:1]([O:3][C:4]([C:5]1[C:28]2[CH2:29][CH2:30][N:25]([C:22]3[CH:23]=[CH:24][C:19]([I:18])=[CH:20][CH:21]=3)[C:26](=[O:37])[C:27]=2[N:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[N:6]=1)=[O:17])[CH3:2]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 21829645Ethyl 2-chloro-2-[2-(4-methoxyphenyl)hydrazono]acetateHCID 222404531-(4-Iodophenyl)-3-morpholino-5,6-dihydropyridin-2(1H)-one

生成物 1

HCID 22240493Ethyl 6-(4-iodophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5-dihydropyrazolo[3,4-c]pyridine-3-carboxylate収率 87%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of chloro[(4-methoxyphenyl)hydrazono]acetic acid ethyl ester (34, 100 g, 0.39 mol) in EtOAc (800 mL) was treated with 1-(4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (10, 150 g, 0.39 mol, 1.0 equiv) at 0–5° C. under N2, and the resulting reaction mixture was treated with triethylamine (TEA, 78.8 g, 109 mL, 0.78 mol, 2.0 equiv) at 0–5° C. under N2. The reaction mixture was then warmed up to room temperature for 30 min before being warmed up to reflux for an additional 6 h. When HPLC and TLC showed that the reaction was complete, the reaction mixture was cooled down to 5–10° C. before being treated dropwise with 4.0 N aqueous HCl solution (488 mL, 1.95 mol, 5.0 equiv) at 0–5° C. The resulting mixture was stirred at 5–20° C. for 4 h. The resulting slurry was then treated with water (400 mL) before being stirred at 5–20° C. for an additional 30 min. The solids were collected by filtration, washed with water (2×200 mL) and 50% of isopropyl acetate/hexane (2×200 mL), dried in vacuo at 40–45° C. for 12 h. The crude desired 1-(4-methoxy-phenyl)-6-(4-iodo-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester (55, 175.5 g, 201.8 g theoretical, 87% for two steps) was obtained as pale-yellow solids, which was found to be essentially pure to do the following reaction without further purification. For 55, CIMS m/z 518 (M++H, C22H20IN3O4).

後処理

  1. customthe resulting reaction mixture
  2. temperaturebefore being warmed up
  3. temperatureto reflux for an additional 6 h
  4. temperaturethe reaction mixture was cooled down to 5–10° C.
  5. stirringbefore being stirred at 5–20° C. for an additional 30 min
  6. filtrationThe solids were collected by filtration
  7. washwashed with water (2×200 mL) and 50% of isopropyl acetate/hexane (2×200 mL)
  8. customdried in vacuo at 40–45° C. for 12 h

出典と根拠

ORDレコード
ord-e1ea60b896524c1d85318b67fb84cb97
出典データセット
uspto-grants-2006_12
特許番号
US07153960B2

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