Diisopropylethylamine → 4-[1-Methyl-2-(4-(trifluoromethyl)phenylamino)-1H-benzoimidazol-5-yloxy]-pyridine-2-carbonitrile

HRID 15091

반응식

HRID 15091 반응식
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6]([N:9]=[C:10]=S)=[CH:5][CH:4]=1.[CH3:14][NH:15][C:16]1[CH:30]=[CH:29][C:19]([O:20][C:21]2[CH:26]=[CH:25][N:24]=[C:23]([C:27]#[N:28])[CH:22]=2)=[CH:18][C:17]=1[NH2:31].CCN(C(C)C)C(C)C.[Cl-].ClC1N(C)CC[NH+]1C>CC#N.O>[CH3:14][N:15]1[C:16]2[CH:30]=[CH:29][C:19]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([C:27]#[N:28])[CH:22]=3)=[CH:18][C:17]=2[N:31]=[C:10]1[NH:9][C:6]1[CH:7]=[CH:8][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:4][CH:5]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 1371344-(Trifluoromethyl)phenyl isothiocyanateHCID 109867151H-Imidazolium, 2-chloro-4,5-dihydro-1,3-dimethyl-, chlorideHCID 210372914-(4-Methylamino-3-amino-phenoxy)-pyridine-2-carbonitrile

생성물 1

HCID 441388984-[1-Methyl-2-(4-(trifluoromethyl)phenylamino)-1H-benzoimidazol-5-yloxy]-pyridine-2-carbonitrile수율 82.8%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

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온도
50 °C

실험 절차

4-(Trifluoromethyl)phenyl isothiocyanate (9.65 g, 0.0475 moles) was added to a solution of 4-(4-methylamino-3-amino-phenoxy)-pyridine-2-carbonitrile (12.0 g, 0.05 moles) in MeCN (60 mL). HPLC analysis indicated complete conversion of the amine after 40 min. The mixture was filtered and the removed solids washed with MeCN (2×12 mL). DIPEA (17.5 mL, 0.1 moles) was added to the filtrate. 2-Chloro-1,3-dimethylimidazolinium chloride (DMC) was added in 4×2.11-g portions (8.44 g, 0.05 moles) every 10 min. After the final addition, the mixture was allowed to stir an additional 10 min when HPLC analysis indicated complete conversion. The mixture was then heated to 50° C. (internal temperature). After 45 min at 50° C., HPLC analysis indicated complete conversion to the product. The mixture was allowed to cool to ambient temperature and then H2O (45 mL) was added. The reaction mixture was initially homogeneous before compound began to precipitate from the mixture. After stirring for 2 h, the solid was collected by filtration and washed with 2:1 MeCN/H2O (2×20 mL). The crude product was dried in a vacuum oven at 50° C. for 16 h to afford 16.10 g (78%) of the title compound 1H NMR (400 MHz, DMSO-d6) δ 9.5 (m, 1 H), 8.5 (m, 1 H), 8.0 (m, 2 H), 7.7 (m, 2H), 7.6 (m, 1H), 7.4 (m, 1 H), 7.3 (m, 1 H), 7.1 (m, 1 H), 6.9 (m, 1 H), 3.7 (m, 3 H); APCI MS [M+H]+=410; HPLC >99% (LCAP).

후처리

  1. customafter 40 min
  2. filtrationThe mixture was filtered
  3. washthe removed solids washed with MeCN (2×12 mL)
  4. additionAfter the final addition
  5. waitAfter 45 min at 50° C.
  6. temperatureto cool to ambient temperature
  7. customto precipitate from the mixture
  8. stirringAfter stirring for 2 h
  9. filtrationthe solid was collected by filtration
  10. washwashed with 2:1 MeCN/H2O (2×20 mL)
  11. dry with materialThe crude product was dried in a vacuum oven at 50° C. for 16 h

출처 및 근거

ORD 기록
ord-0f0b4155d88a411bb087e52e9889f3d2
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732465B2

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