Triphenylphosphine → 6-[1-(tert-butoxycarbonyl)piperidin-4-yl]methoxy-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazoline

HRID 916469노트

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HRID 916469 반응식
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:23][CH3:24])=[C:19]([OH:22])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.O[CH2:26][CH:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[C:36]([O:35][C:33]([N:30]1[CH2:31][CH2:32][CH:27]([CH2:26][O:22][C:19]2[CH:20]=[C:21]3[C:16](=[CH:17][C:18]=2[O:23][CH3:24])[N:15]=[CH:14][N:13]=[C:12]3[O:11][C:10]2[C:2]([F:1])=[C:3]3[C:7](=[CH:8][CH:9]=2)[NH:6][CH:5]=[CH:4]3)[CH2:28][CH2:29]1)=[O:34])([CH3:39])([CH3:37])[CH3:38]

참가 물질

6

반응물 4

HCID 11776Triphenylphosphine2회HCID 75555Diisopropyl diazene-1,2-dicarboxylate2회HCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate2회HCID 589602194-[(4-fluoro-1H-indol-5-yl)oxy]-6-hydroxy-7-methoxyquinazoline

생성물 1

HCID 670192356-[1-(tert-butoxycarbonyl)piperidin-4-yl]methoxy-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazoline수율 76%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

A mixture of 4-[(4-fluoro-1H-indol-5-yl)oxy]-6-hydroxy-7-methoxyquinazoline (250 mg, 0.77 mmol), (prepared as described for the starting material in Example 10), tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (199 mg, 0.92 mmol), (prepared as described for the starting material in Example 11), and triphenylphosphine (242 mg, 0.92 mmol) in dichloromethane (15 ml) was stirred and cooled to 0° C. Diisopropyl azodicarboxylate (182 μl, 0.92 mmol) in dichloromethane (2 ml) was added. The mixture was stirred for 3 hours and then a further 0.5 mole equivalent of tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate, triphenylphosphine and diisopropyl azodicarboxylate added. The mixture was stirred for 1 hour and then concentrated under reduced pressure. The residue was purified by column chromatography eluting with ethyl acetate/hexane (1/1) followed by methylene chloride/methanol (99/1) to give 6-[1-(tert-butoxycarbonyl)piperidin-4-yl]methoxy-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazoline (306 mg containing 10% w/w triphenylphosphine oxide) which was used without further purification in the next step.

후처리

  1. custom(prepared
  2. custom(prepared
  3. stirringThe mixture was stirred for 3 hours
  4. stirringThe mixture was stirred for 1 hour
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography
  7. washeluting with ethyl acetate/hexane (1/1)

출처 및 근거

ORD 기록
ord-36e650529ed14c24a97f6a4967386a0b
출처 데이터셋
uspto-grants-2007_09
특허 번호
US07268230B2

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