Triphenylphosphine → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-morpholinoethoxy)ethoxy)quinazoline hydrochloride

HRID 1838586ノート

反応式

HRID 1838586 の反応式
N(C(OCC)=O)=NC(OCC)=O.[Cl:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([OH:31])=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O:54]1[CH2:59][CH2:58][N:57]([CH2:60][CH2:61][O:62][CH2:63][CH2:64]O)[CH2:56][CH2:55]1>C(Cl)Cl>[ClH:13].[Cl:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:31][CH2:64][CH2:63][O:62][CH2:61][CH2:60][N:57]4[CH2:58][CH2:59][O:54][CH2:55][CH2:56]4)=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1

参加物

6

反応物 4

HCID 11776Triphenylphosphine2 回HCID 220568ethyl N-ethoxycarbonyliminocarbamate2 回HCID 4584644-(2-(2-Hydroxyethoxy)ethyl)morpholine2 回HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

生成物 1

HCID 187534504-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-morpholinoethoxy)ethoxy)quinazoline hydrochloride収率 97.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Diethyl azodicarboxylate (209 mg, 1.2 mmol) was added dropwise to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (128 mg, 0.4 mmol), (prepared as described for the starting material in Example 2), triphenylphosphine (314 mg, 1.2 mmol) and 2-(2-morpholinoethoxy)ethanol (97 mg, 0.56 mmol) in methylene chloride (4 ml) under nitrogen. The mixture was stirred for 1 hour at ambient temperature, triphenylphosphine (105 mg, 0.4 mmol), 2-(2-morpholinoethoxy)ethanol (49 mg, 0.28 mmol) and diethyl azodicarboxylate (70 mg, 0.4 mmol) were added. The mixture was stirred for 1 hour at ambient temperature and was purified by pouring directly onto a silica column eluting with methylene chloride/acetonitrile/methanol (6/3/1). The purified product was triturated with ether, collected by filtration and dissolved in methylene chloride. 2M Ethereal hydrogen chloride (0.5 ml) was added and the resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-morpholinoethoxy)ethoxy)quinazoline hydrochloride (100 mg, 45%).

後処理

  1. custom(prepared
  2. stirringThe mixture was stirred for 1 hour at ambient temperature
  3. customwas purified
  4. additionby pouring directly onto a silica column
  5. washeluting with methylene chloride/acetonitrile/methanol (6/3/1)
  6. customThe purified product was triturated with ether
  7. filtrationcollected by filtration
  8. dissolutiondissolved in methylene chloride
  9. addition2M Ethereal hydrogen chloride (0.5 ml) was added
  10. filtrationthe resulting precipitate was collected by filtration
  11. washwashed with ether
  12. customdried under vacuum

出典と根拠

ORDレコード
ord-562bc65a3db34b58a657c1355b03ff66
出典データセット
uspto-grants-2004_01
特許番号
US06673803B2

反応ノート

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