Dimethylformamide → 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 525693ノート

反応式

HRID 525693 の反応式
CN(C=O)C.O=S(Cl)Cl.[Cl:10][C:11]1[N:16]=[CH:15][C:14]([C:17]([OH:19])=O)=[CH:13][C:12]=1[I:20].CCN(C(C)C)C(C)C.[F:30][C:31]([F:41])([F:40])[O:32][C:33]1[CH:39]=[CH:38][C:36]([NH2:37])=[CH:35][CH:34]=1>C1(C)C=CC=CC=1.C1COCC1.CC(OC)(C)C>[Cl:10][C:11]1[C:12]([I:20])=[CH:13][C:14]([C:17]([NH:37][C:36]2[CH:38]=[CH:39][C:33]([O:32][C:31]([F:30])([F:40])[F:41])=[CH:34][CH:35]=2)=[O:19])=[CH:15][N:16]=1

参加物

9

反応物 5

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 6008484-(Trifluoromethoxy)anilineHCID 222714776-Chloro-5-iodonicotinic acid

生成物 1

HCID 867025996-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

試薬・触媒・溶媒 3

HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒HCID 15413tert-Butyl methyl ether溶媒

反応条件

温度
80 °C

実験手順

DMF (1.927 mL, 24.89 mmol) and SOCl2 (18.17 mL, 249 mmol) were added to a suspension of 6-chloro-5-iodo-3-pyridinecarboxylic acid (24 g, 83 mmol) in toluene (165 mL) and the RM was stirred at 80° C. for 1 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in THF (165 mL). DIPEA (29.0 mL, 166 mmol) was added, the mixture was cooled down to −15° C., treated dropwise with a solution of 4-(trifluoromethoxy)aniline (15.43 g, 87 mmol) in THF (165 mL) and stirred at RT for 1 h. The solvent was off under reduced pressure and the residue was dissolved in TBME (500 mL), washed with 1 M HCl, a sat. aq. solution of NaHCO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure and the product was recrystallized from EtOAc/n-heptane to afford the title compound as a white solid. HPLC (Condition 4) tR=6.36 min, UPLC-MS (Condition 3) tR=1.23 min, m/z=441.1 [M−H]−.

後処理

  1. customThe solvent was evaporated off under reduced pressure
  2. dissolutionthe residue was dissolved in THF (165 mL)
  3. temperaturethe mixture was cooled down to −15° C.
  4. stirringstirred at RT for 1 h
  5. washwashed with 1 M HCl
  6. dry with materiala sat. aq. solution of NaHCO3 and brine, dried over Na2SO4
  7. customthe solvent was evaporated off under reduced pressure
  8. customthe product was recrystallized from EtOAc/n-heptane

出典と根拠

ORDレコード
ord-80ab45fbd40f4bfe91a17c4b9d481e0c
出典データセット
uspto-grants-2016_05
特許番号
US09340537B2

反応ノート

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