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

HRID 450173노트

반응식

HRID 450173 반응식
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=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.C(O)(=O)C>C1COCC1.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:3]=[N:4][CH:5]=[N:6][CH:7]=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 4

HCID 176Acetic AcidHCID 344373Pyrimidin-5-amineHCID 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 498693544-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(5-pyrimidinyl)-1,3,5-triazin-2-amine수율 47%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To 0.186 g (1.96 mmol) of 5-aminopyrimidine in THF (4 mL) was added 1.1 mL of NaHMDS (2 M solution in THF) at 0° C. 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 (5 mL) was added and the resulting mixture WAS stirred for 1 hr at room temperature. The resulting mixture was neutralized with acetic acid, diluted with water, and extracted with EtOAc. The organic layer was washed with water, and aq. NH3, and dried. Removal of the solvent, followed by chromatography on alumina, eluting with CH2Cl2/EtOAc (1:9), then CH2Cl2/EtOAc (1:3), gave an off-white powder. Recrystallization from ethanol gave 0.123 g (47% yield) of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(5-pyrimidinyl)-1,3,5-triazin-2-amine: mp 290-292° C.; 1H NMR (CDCl3) δ9.07 (s, 2H), 9.02 (s, 1H), 8.37 (d, J=7.2 Hz, 1H), 7.89 (dd, J=7.7, 1.5 Hz, 1H), 7.57 (t, JHF=53.7 Hz, 1H), 7.47-7.40 (m, 2H), 7.11 (s, 1H), 3.95-3.92 (m, 4H), 3.83 (br s, 4H); Anal. Calcd. for C19H17F2N9O: C, 53.65; H, 4.0; N, 29.6. Found: C, 53.4; H, 4.2; N, 29.4%.

후처리

  1. stirringthe resulting mixture WAS stirred for 1 hr at room temperature
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water, and aq. NH3
  4. customdried
  5. customRemoval of the solvent
  6. washeluting with CH2Cl2/EtOAc (1:9)
  7. customCH2Cl2/EtOAc (1:3), gave an off-white powder
  8. customRecrystallization from ethanol

출처 및 근거

ORD 기록
ord-488d03b94ac04662a3bfcfac3fad83a0
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486939B2

반응 노트

불러오는 중…