Triphenylphosphine → tert-Butyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl]oxy)-2-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate

HRID 1443009ノート

反応式

HRID 1443009 の反応式
CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C.[Cl:17][C:18]1[CH:19]=[C:20]([CH:35]=[CH:36][C:37]=1[F:38])[NH:21][C:22]1[C:31]2[C:30]([OH:32])=[CH:29][C:28]([O:33][CH3:34])=[CH:27][C:26]=2[N:25]=[CH:24][N:23]=1.[Si:39]([O:46][C@H:47]1[CH2:51][N:50]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C@H:49]([CH2:59]O)[CH2:48]1)([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Si:39]([O:46][C@H:47]1[CH2:51][N:50]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C@H:49]([CH2:59][O:32][C:30]2[CH:29]=[C:28]([O:33][CH3:34])[CH:27]=[C:26]3[C:31]=2[C:22]([NH:21][C:20]2[CH:35]=[CH:36][C:37]([F:38])=[C:18]([Cl:17])[CH:19]=2)=[N:23][CH:24]=[N:25]3)[CH2:48]1)([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40]

参加物

6

反応物 4

HCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 11078078tert-butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylateHCID 1363475184-[3-Chloro-4-fluoroanilino]-7-methoxyquinazolin-5-ol

生成物 1

HCID 86607807tert-Butyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl]oxy)-2-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate収率 70%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Di-tert-butylazodicarboxylate (DTAD, 692 mg) was added in one portion to a mixture of 4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-ol (640 mg), tert-butyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)-pyrrolidine-1-carboxylate (830 mg), and triphenylphosphine (788 mg) in DCM (50 ml) at room temperature, under an atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 24 hours and then concentrated in vacuo to leave a brown oil. Purification by column chromatography, using 0-50% ethyl acetate in hexane as eluent, gave tert-butyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl]-oxy}-2-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]-pyrrolidine-1-carboxylate as a white solid (884 mg, 70%); Mass spectrum MH+ 633.

後処理

  1. concentrationconcentrated in vacuo
  2. customto leave a brown oil
  3. customPurification by column chromatography

出典と根拠

ORDレコード
ord-96c36f8fcc4d4d28900f6c1808d3c3eb
出典データセット
uspto-grants-2010_02
特許番号
US07659279B2

反応ノート

読み込み中…