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4-Methylmorpholine → 4-[(3-Bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]-6-[(1-oxo-2,4-hexadien-1-yl)amino]quinazoline

HRID 1023294
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HRID 1023294 반응식
[C:1](O)(=[O:7])/[CH:2]=[CH:3]/[CH:4]=[CH:5]/[CH3:6].ClC(OCC(C)C)=O.CN1CCOCC1.[NH2:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:34]=1[O:35][CH2:36][CH2:37][CH2:38][CH:39]1[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]1)[N:31]=[CH:30][N:29]=[C:28]2[NH:46][C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([Br:53])[CH:48]=1>O1CCCC1.N1C=CC=CC=1>[Br:53][C:49]1[CH:48]=[C:47]([NH:46][C:28]2[C:27]3[C:32](=[CH:33][C:34]([O:35][CH2:36][CH2:37][CH2:38][CH:39]4[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]4)=[C:25]([NH:24][C:1](=[O:7])[CH:2]=[CH:3][CH:4]=[CH:5][CH3:6])[CH:26]=3)[N:31]=[CH:30][N:29]=2)[CH:52]=[CH:51][CH:50]=1
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참가 물질

7

반응물 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 643460Sorbic AcidHCID 111906016-Amino-4-[(3-bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]quinazoline

생성물 1

HCID 537025584-[(3-Bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]-6-[(1-oxo-2,4-hexadien-1-yl)amino]quinazoline

시약·촉매·용매 2

HCID 1049
Pyridine
용매
HCID 8028Tetrahydrofuran용매

실험 절차

To 31 mg of sorbic acid in 1 ml of tetrahydrofuran are added 40 μl of isobutyl chloroformate followed by 45 μl of N-methylmorpholine whilst cooling with an ice bath. The white suspension is stirred for one minute, then a solution of 100 mg of 6-amino-4-[(3-bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]quinazoline in 1.5 ml of pyridine is added. The ice bath is removed and the reaction mixture is stirred overnight. For working up, it is poured onto 20 ml of ice water, stirred for 30 minutes and adjusted to pH 9-10 with a few drops of 2 N sodium hydroxide solution. The aqueous phase is extracted with methylene chloride, the combined organic phases are dried over sodium sulfate and concentrated by evaporation. The resin-like crude product is purified by chromatography over an aluminium oxide column (activity III) with methylene chloride/methanol (99.5:0.5). Yield: 62 mg (52% of theory); Rf value: 0.29 (aluminium oxide, activity III; methylene chloride/methanol=98:2); mass spectrum (EI): m/z=563, 565 [M]+.

후처리

  1. temperaturewhilst cooling with an ice bath
  2. customThe ice bath is removed
  3. stirringthe reaction mixture is stirred overnight
  4. additionit is poured onto 20 ml of ice water
  5. stirringstirred for 30 minutes
  6. extractionThe aqueous phase is extracted with methylene chloride
  7. dry with materialthe combined organic phases are dried over sodium sulfate
  8. concentrationconcentrated by evaporation
  9. customThe resin-like crude product is purified by chromatography over an aluminium oxide column (activity III) with methylene chloride/methanol (99.5:0.5)

출처 및 근거

ORD 기록
ord-04c9b8b8f214439f9d1842022ef96776
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08722694B2

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