Diisopropylethylamine → 3-(4-((2-(1H-imidazol-5-yl)acetamido)methyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamate

HRID 2098384

반응식

HRID 2098384 반응식
[NH:1]1[C:5]([CH2:6][C:7]([OH:9])=O)=[CH:4][N:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH3:43][N:44]([CH3:75])[C:45](=[O:74])[O:46][C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([NH:53][C:54]([C:56]2([CH2:72][NH2:73])[CH2:61][CH2:60][N:59]([C:62]3[C:63]4[C:70]([CH3:71])=[CH:69][NH:68][C:64]=4[N:65]=[CH:66][N:67]=3)[CH2:58][CH2:57]2)=[O:55])[CH:48]=1>C(Cl)Cl.O>[CH3:75][N:44]([CH3:43])[C:45](=[O:74])[O:46][C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([NH:53][C:54]([C:56]2([CH2:72][NH:73][C:7](=[O:9])[CH2:6][C:5]3[NH:1][CH:2]=[N:3][CH:4]=3)[CH2:57][CH2:58][N:59]([C:62]3[C:63]4[C:70]([CH3:71])=[CH:69][NH:68][C:64]=4[N:65]=[CH:66][N:67]=3)[CH2:60][CH2:61]2)=[O:55])[CH:48]=1

참가 물질

7

반응물 4

HCID 81531Diisopropylethylamine2회HCID 96215Imidazole-4-acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 56962369Lx-7101

생성물 1

HCID 444821143-(4-((2-(1H-imidazol-5-yl)acetamido)methyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamate수율 72%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매3회

실험 절차

To a suspension of 2-(1H-imidazol-5-yl)acetic acid (0.238 g, 1.47 mmol) and HATU (0.372 g, 0.978 mmol) in CH2Cl2 (5 mL) was added N,N-diisopropylethylamine (0.51 mL, 2.93 mmol). The resulting solution was allowed to stir for 20 min. at room temperature. To this solution was added the acetate salt of 3-(4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamate (from example 20, 0.500 g, 0.978 mmol) and N,N-diisopropylethylamine (0.17 mL) in CH2Cl2 (5 mL). The reaction was allowed to stir at room temperature for 6 h, and then diluted with H2O (10 mL) and CH2Cl2 (20 mL). The mixture was extracted with CH2Cl2 (2×10 mL), and the combined organics were washed with NaHCO3 (10 mL) and brine (10 mL), dried over MgSO4, and concentrated under vacuum. The residue was purified by flash chromatography (3-10% MeOH:CH2Cl2) to afford the title compound (0.393 g, 72% yield) as a white solid. This solid was suspended in water, and acetic acid was added until the solution became clear. This solution was frozen and lyophilized to the di-acetate salt of the title compound (0.477 g).

후처리

  1. stirringto stir at room temperature for 6 h
  2. extractionThe mixture was extracted with CH2Cl2 (2×10 mL)
  3. washthe combined organics were washed with NaHCO3 (10 mL) and brine (10 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by flash chromatography (3-10% MeOH:CH2Cl2)

출처 및 근거

ORD 기록
ord-70e795e363ae43bb9d85857716e1094d
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08450332B2

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