Pyrimidin-5-amine → HCID 49869918, 화합물

HRID 450169

반응식

HRID 450169 반응식
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.C([Li])CCC.Cl[C:14]1[N:19]=[C:18]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:17]=[C:16]([N:26]2[C:30]3[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:29]=3[N:28]=[C:27]2[CH:37]([F:39])[F:38])[N:15]=1>C1COCC1.C(O)(=O)C.O>[F:39][CH:37]([F:38])[C:27]1[N:26]([C:16]2[N:17]=[C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:19]=[C:14]([NH:1][C:2]3[CH:3]=[N:4][CH:5]=[N:6][CH:7]=3)[N:15]=2)[C:30]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:29]=2[N:28]=1

참가 물질

7

반응물 3

HCID 344373Pyrimidin-5-amineHCID 534881021-[4-Chloro-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 178418339Butyllithium

생성물 1

HCID 49869918HCID 49869918, 화합물수율 22.6%

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To 0.207 g (2.18 mmol) of 5-aminopyrimidine in THF (4 mL) was added 0.96 mL of n-butyllithium (2.5 M solution in hexanes) and the mixture stirred for 10 min. A solution of 0.260 g (0.66 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (Example 2) in THF (5 mL) was added. The resulting mixture was stirred at room temperature for 1 hr. After neutralization with acetic acid, the mixture was diluted with water, and extracted with EtOAc. The organic layer was washed successively with water and aqueous NH3, and dried. Removal of the solvent, followed by chromatography on silica eluting with hexanes/EtOAc (1:1) gave a yellow powder. Recrystallization from ethanol/CH2Cl2 gave 0.068 g (20% yield) of 4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(5-pyrimidinyl)-1,3,5-triazin-2-amine: mp 293-295° C.; 1H NMR (CDCl3) δ 9.07 (s, 2H), 9.01 (s, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.48 (t, JHF=53.2 Hz, 1H), 7.37 (t, J=8.2 Hz, 1H), 7.14 (s, 1H), 6.84 (d, J=8.0 Hz, 1H), 4.05 (s, 3H), 3.95-3.90 (m, 4H), 3.82-3.81 (m, 4H); Anal. Calcd. for C20H19F2N9O2: C, 52.75; H, 4.2; N, 27.7. Found: C, 52.9; H, 4.2; N, 27.7%.

후처리

  1. stirringThe resulting mixture was stirred at room temperature for 1 hr
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed successively with water and aqueous NH3
  4. customdried
  5. customRemoval of the solvent
  6. customgave a yellow powder
  7. customRecrystallization from ethanol/CH2Cl2

출처 및 근거

ORD 기록
ord-ef3c1590b1ad4e2386b3211d43f5bde9
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486939B2

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