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 1443001노트

반응식

HRID 1443001 반응식
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]

참가 물질

6

반응물 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

생성물 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-carboxylate수율 59%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-70c83045ed484247b1f75e775cb6f000
출처 데이터셋
uspto-grants-2010_02
특허 번호
US07659279B2

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