Tributylphosphine → 7-(3-Benzyloxypropoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride

HRID 279668

反応式

HRID 279668 の反応式
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:19][C:20]1[CH:39]=[CH:38][C:23]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([OH:37])=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)=[C:22]([F:40])[CH:21]=1.[CH2:41]([O:48][CH2:49][CH2:50][CH2:51]O)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl.CCOCC>[ClH:19].[CH2:41]([O:48][CH2:49][CH2:50][CH2:51][O:37][C:31]1[CH:30]=[C:29]2[C:34]([C:25]([NH:24][C:23]3[CH:38]=[CH:39][C:20]([Cl:19])=[CH:21][C:22]=3[F:40])=[N:26][CH:27]=[N:28]2)=[CH:33][C:32]=1[O:35][CH3:36])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

参加物

7

反応物 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 3479713-Benzyloxy-1-propanolHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

生成物 1

HCID 226248927-(3-Benzyloxypropoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride収率 56.6%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
5 °C

実験手順

1,1′-(azodicarbonyl)dipiperidine (480 mg, 1.9 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (200 mg, 0.63 mmol), 3-benzyloxypropanol (150 μl, 0.95 mmol) and tributylphosphine (459 μl, 1.86 mmol) in methylene chloride (20 ml) at 5° C. The reaction was stirred for 1 hour at 5° C. and then for 18 hours at ambient temperature. The mixture was diluted with ether and stirred for 15 minutes. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was partitioned between ethyl acetate and water, and the organic layer was separated, dried (MgSO4) and the solvent removed by evaporation. A 1M solution of ethereal hydrogen chloride was added to the residue, the resulting solution was reduced in volume by evaporation and the resulting precipitate was collected by filtration and dried to give 7-(3-benzyloxypropoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (90 mg, 31%).

後処理

  1. waitfor 18 hours at ambient temperature
  2. stirringstirred for 15 minutes
  3. customThe insolubles were removed by filtration
  4. customthe volatiles were removed from the filtrate by evaporation
  5. customThe residue was partitioned between ethyl acetate and water
  6. customthe organic layer was separated
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. additionA 1M solution of ethereal hydrogen chloride was added to the residue
  10. customthe resulting solution was reduced in volume by evaporation
  11. filtrationthe resulting precipitate was collected by filtration
  12. customdried

出典と根拠

ORDレコード
ord-375f564676b4499f817493dc5998a5e9
出典データセット
uspto-grants-2002_03
特許番号
US06362336B1

関連ノート

読み込み中…