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

HRID 535746노트

반응식

HRID 535746 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

반응 조건

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-3d887c1cc4104f8097d826ffeb6b2a1d
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08859548B2

반응 노트

불러오는 중…