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

HRID 450134

反応式

HRID 450134 の反応式
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[CH:23]([F:25])[F:24])[N:3]=1.[NH2:26][C:27]1[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=1.[Li+].CC([N-]C(C)C)C.CC(O)=O>C1COCC1.O>[F:24][CH:23]([F:25])[C:15]1[N:14]([C:4]2[N:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:7]=[C:2]([NH:26][C:27]3[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=3)[N:3]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 100093-AminopyridineHCID 2724682Lithium diisopropylamideHCID 220368724-(4-chloro-6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazin-2-yl)morpholine

生成物 1

HCID 498689424-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(3-pyridinyl)-1,3,5-triazin-2-amine収率 43%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

1-[4-Chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole (U.S. Pat. Appl. Publ. No. US 2007/244110) (0.183 g, 0.5 mmol) was added to a mixture of 3-aminopyridine (0.20 g, 2 mmol) and LDA (1.0 mL, 2 M in THF, 2 mmol) in 10 mL THF at room temperature. After 5 min, the mixture was neutralized with HOAc, diluted with water, extracted with EtOAc, and dried (Na2SO4). Chromatography on alumina eluting with CH2Cl2/EtOAc (4:1) gave a solid, which was recrystallized from i-Pr2O to give 92 mg (43% yield) of (4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-N-(3-pyridinyl)-1,3,5-triazin-2-amine: mp (i-Pr2O) 228-230° C.; 1H NMR (CDCl3) δ 8.86 (br, 1H), 8.42 (d, J=2.0 Hz, 1H), 8.38 (d, J=6.2 Hz, 1H), 7.98 (d, J=8.2 Hz, 1H), 7.89 (dd, J=6.2, 2.9 Hz, 1H), 7.58 (br t, JHF=53.8 Hz, 1H), 7.42 (m, 2H), 7.34 (dd, J=8.3, 4.7 Hz, 1H), 7.28 (m, exchangeable with D2O, 1H), 3.93 (m, 4H), 3.82 (m, 4H); Anal. Calcd. for C20H18F2N8O: C, 56.6; H, 4.3; N, 26.4. Found: C, 56.5; H, 4.4; N, 26.1%.

後処理

  1. extractionextracted with EtOAc
  2. dry with materialdried (Na2SO4)
  3. customChromatography on alumina eluting with CH2Cl2/EtOAc (4:1) gave a solid, which
  4. customwas recrystallized from i-Pr2O

出典と根拠

ORDレコード
ord-e53670de32254dd89df33fa3d0ed1482
出典データセット
uspto-grants-2013_07
特許番号
US08486939B2

関連ノート

読み込み中…