Sodium Carbonate → 1-((4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)methyl)cyclopropanecarbonitrile

HRID 885743노트

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HRID 885743 반응식
[NH2:1][CH2:2][C:3]1([C:6]#[N:7])[CH2:5][CH2:4]1.[Br:8][C:9]1[N:10]=[C:11]([CH:29]2[CH2:31][CH2:30]2)[N:12]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:13]=1[C:14]1[CH:19]=[CH:18][N:17]=[C:16](Cl)[N:15]=1.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[Na+].[Na+]>CN1C(=O)CCC1>[Br:8][C:9]1[N:10]=[C:11]([CH:29]2[CH2:31][CH2:30]2)[N:12]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:27])[CH3:28])[C:13]=1[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([NH:7][CH2:6][C:3]2([C:2]#[N:1])[CH2:5][CH2:4]2)[N:15]=1

참가 물질

6

반응물 4

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 552821201-(Aminomethyl)cyclopropanecarbonitrileHCID 866514084-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)-2-chloropyrimidine

생성물 1

HCID 698095911-((4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)methyl)cyclopropanecarbonitrile수율 66%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

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온도
110 °C

실험 절차

A mixture of 1-(aminomethyl)cyclopropanecarbonitrile (0.67 g, 7.0 mmol), 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (2.01 g, 4.7 mmol), DIEA (1.64 ml, 9.35 mmol), Na2CO3 (0.99 g, 9.4 mmol) and NMP (2 mL) was heated at 110° C. for 25 hours. The reaction mixture was allowed to cool to room temperature and partitioned between EtOAc (10 mL) and water (20 mL). The layers were separated and the organic portion was sequentially washed with water (20 mL), brine (10 mL), and concentrated. The resulting residue was purified by flash chromatography on silica gel eluting with an EtOAc-heptane (0-50%) gradient to provide 1-((4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)methyl)cyclopropanecarbonitrile (1.50 g, 3.06 mmol, 66%) as a white foam. LCMS(m/z) 491.1 (MH+), tR=0.99 minute.

후처리

  1. temperatureto cool to room temperature
  2. custompartitioned between EtOAc (10 mL) and water (20 mL)
  3. customThe layers were separated
  4. washthe organic portion was sequentially washed with water (20 mL), brine (10 mL)
  5. concentrationconcentrated
  6. customThe resulting residue was purified by flash chromatography on silica gel eluting with an EtOAc-heptane (0-50%) gradient

출처 및 근거

ORD 기록
ord-5941120f995d4fceab89e843fe7bc5c4
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08242260B2

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