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

HRID 1443001ノート

反応式

HRID 1443001 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]([NH:25][C:26]2[C:35]3[C:34]([OH:36])=[CH:33][C:32]([O:37][CH3:38])=[CH:31][C:30]=3[N:29]=[CH:28][N:27]=2)[CH:21]=[CH:22][C:23]=1[F:24].[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>[C:42]([Si:39]([CH3:41])([CH3:40])[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:36][C:34]2[CH:33]=[C:32]([O:37][CH3:38])[CH:31]=[C:30]3[C:35]=2[C:26]([NH:25][C:20]2[CH:21]=[CH:22][C:23]([F:24])=[C:18]([Cl:17])[CH:19]=2)=[N:27][CH:28]=[N:29]3)[CH2:48]1)([CH3:44])([CH3:45])[CH3:43]

参加物

6

反応物 4

HCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 66962096tert-butyl (2R,4S)-4-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylateHCID 1363475184-[3-Chloro-4-fluoroanilino]-7-methoxyquinazolin-5-ol

生成物 1

HCID 86607805tert-butyl (2R,4S)-4-{[tert-butyl-(dimethyl)silyl]-oxy}-2-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]-pyrrolidine-1-carboxylate収率 59%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Di-tert-butylazodicarboxylate (DTAD, 623 mg) was added in one portion to a mixture of 4-[(3-chloro-4-fluorophenyl)-amino]-7-methoxy-quinazolin-5-ol (578 mg, prepared as described in Example 1, preparation of starting materials), tert-butyl (2R,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)pyrrolidine-1-carboxylate (750 mg), and triphenylphosphine (710 mg) in DCM (100 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 (2R,4S)-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 (671 mg, 59%); NMR spectrum (DMSO-d6) 8.46 (s, 1H), 8.03 (br s, 1H), 7.67 (br s, 1H), 7.43 (t, 1H), 6.85-6.81 (m, 2H), 4.57-4.20 (m, 4H), 3.94 (s, 3H), 3.47-3.40 (m, 1H), 2.10-2.00 (m, 2H), 1.33 (m, 10H), 0.86 (s, 9H), 0.07 (s, 6H); 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-70c83045ed484247b1f75e775cb6f000
出典データセット
uspto-grants-2010_02
特許番号
US07659279B2

反応ノート

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