Tetrahydrofuran → HCID 57955165、化合物

HRID 1094885ノート

反応式

HRID 1094885 の反応式
[NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]4[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=4[F:36])=[O:24])=[CH:18][CH:17]=3)[C:9]([CH2:13][O:14][CH3:15])=[C:10]([CH2:11][OH:12])[N:6]2[N:5]=[CH:4][N:3]=1.O=S(Cl)Cl.[CH2:41]1COCC1>C(Cl)Cl>[NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([NH:25][C:26]4[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[CH:28][C:27]=4[F:36])=[O:24])=[CH:18][CH:17]=3)[C:9]([CH2:13][O:14][CH3:15])=[C:10]([CH2:11][O:12][CH3:41])[N:6]2[N:5]=[CH:4][N:3]=1

参加物

5

反応物 3

HCID 8028TetrahydrofuranHCID 24386Thionyl Chloride2 回HCID 57955156HCID 57955156、化合物

生成物 1

HCID 57955165HCID 57955165、化合物収率 53%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of Example 23 (N-{4-[4-amino-7-(hydroxymethyl)-6-(methoxy-methyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoro-methyl)-phenyl]urea (22 mg, 0.04 mmol)) in anhydrous THF (1 mL) and CH2Cl2 (1 mL) was added SOCl2 (0.006 ml, 0.08 mmol). After 20 min, analytical HPLC showed half of the starting material remained. Additional SOCl2 (0.01 ml) was added and the reaction was stirred at rt for 2.5 h until completion. The mixture was evaporated to dryness and CH2Cl2 (3 ml) was added. The solvent was evaporated to dryness and the crude concentrate was re-suspended in CH2Cl2 and evaporated to remove the excess SOCl2 completely. To the resulting solid was added anhydrous MeOH (1 ml) and Hunig's base (0.008 ml), the reaction was stirred at 70° C. overnight. After 16 h, the reaction was cooled to rt and solvent was evaporated. The crude material was taken up in ethyl acetate, washed with aq. saturated sodium bicarbonate three times and dried over Na2SO4. After concentration, the resulting crude was purified via column chromatography (5:95 v/v MeOH—CH2Cl2) to afford 12 mg of the title compound (yield 53%). 1H-NMR (DMSO-d6) 9.32 (s, 1H), 8.96 (d, J=3 Hz, 1H), 8.63 (dd, J=7, 3 Hz, 1H), 7.92 (s, 1H), 7.59 (t, J=3 Hz, 2H), 7.57 to 7.32 (m, 4H), 4.73 (s, 2H), 4.28 (s, 2H), 3.26 (s, 3H), 3.24 (s, 3H) ppm; MS [M+H]+=519.1; LCMS RT=2.84 rain

後処理

  1. customThe mixture was evaporated to dryness and CH2Cl2 (3 ml)
  2. additionwas added
  3. customThe solvent was evaporated to dryness
  4. concentrationthe crude concentrate
  5. customevaporated
  6. customto remove the excess SOCl2 completely
  7. additionTo the resulting solid was added anhydrous MeOH (1 ml) and Hunig's base (0.008 ml)
  8. stirringthe reaction was stirred at 70° C. overnight
  9. waitAfter 16 h
  10. temperaturethe reaction was cooled to rt
  11. customsolvent was evaporated
  12. washwashed with aq. saturated sodium bicarbonate three times
  13. dry with materialdried over Na2SO4
  14. concentrationAfter concentration
  15. customthe resulting crude was purified via column chromatography (5:95 v/v MeOH—CH2Cl2)

出典と根拠

ORDレコード
ord-42eea51e86754942b8450cf1a4bcd8eb
出典データセット
uspto-grants-2012_03
特許番号
US08133995B2

反応ノート

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