Aminopyrazine → 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(2-pyrazinyl)-1,3,5-triazin-2-amine

HRID 450158

반응식

HRID 450158 반응식
[NH2:1][C:2]1[CH:7]=[N:6][CH:5]=[CH:4][N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl[C:19]1[N:24]=[C:23]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[N:22]=[C:21]([N:31]2[C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=3[N:33]=[C:32]2[CH:40]([F:42])[F:41])[N:20]=1>C1COCC1.C(O)(=O)C.O>[F:42][CH:40]([F:41])[C:32]1[N:31]([C:21]2[N:22]=[C:23]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[N:24]=[C:19]([NH:1][C:2]3[CH:7]=[N:6][CH:5]=[CH:4][N:3]=3)[N:20]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[N:33]=1

참가 물질

7

반응물 3

HCID 78747AminopyrazineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 220368724-(4-chloro-6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazin-2-yl)morpholine

생성물 1

HCID 581027874-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(2-pyrazinyl)-1,3,5-triazin-2-amine수율 61.5%

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of 0.219 g (2.30 mmol) of aminopyrazine in THF (5 mL) at 0° C. was added 1.3 mL of NaHMDS (2 M solution in THF), and the mixture was stirred for 15 min. A solution of 0.238 g (0.65 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole in THF (6 mL) was added, and the resulting mixture was stirred for 1 hr at RT. After neutralization with acetic acid, the mixture was diluted with water and extracted with EtOAc. The organic layer was washed sequentially with water and aq. NH3, dried and concentrated. Chromatography on alumina, eluting first with hexanes/EtOAc (1:1) and then with CH2Cl2/EtOAc (1:4) to CH2Cl2/EtOAc (1:1) gave a white powder. Recrystallization from ethanol/CH2Cl2 gave 0.170 g (54% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(2-pyrazinyl)-1,3,5-triazin-2-amine: mp 271-274° C.; 1H NMR (CDCl3) δ9.59 (s, 1H), 8.42-8.33 (m, 3H), 7.92 (d, J=7.4 Hz, 1H), 7.81 (s, 1H), 7.60 (t, JHF=53.5 Hz, 1H), 7.48-7.41 (m, 2H), 3.98 (d, J=4.2 Hz, 4H), 3.85 (d, J=4.2 Hz, 4H); Anal. Calcd. for C19H17F2N9O: C, 53.65; H, 4.1; N, 29.6. Found: C, 53.9; H, 3.8; N, 29.7%.

후처리

  1. stirringthe resulting mixture was stirred for 1 hr at RT
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed sequentially with water and aq. NH3
  4. customdried
  5. concentrationconcentrated
  6. washChromatography on alumina, eluting first with hexanes/EtOAc (1:1)
  7. customwith CH2Cl2/EtOAc (1:4) to CH2Cl2/EtOAc (1:1) gave a white powder
  8. customRecrystallization from ethanol/CH2Cl2

출처 및 근거

ORD 기록
ord-05e5811baa754bd59ab42d296d37a12f
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486939B2

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