Sodium Hydroxide → 3-(2-Fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid amide

HRID 2264962ノート

反応式

HRID 2264962 の反応式
C[O:2][C:3]([C:5]1[N:13]([CH2:14][CH2:15][O:16][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH:27][C:28]1[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:29]=1[F:35])=O.[OH-].[Na+].[Cl-].[NH4+].C([N:43](C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(O)C>[F:35][C:29]1[CH:30]=[C:31]([I:34])[CH:32]=[CH:33][C:28]=1[NH:27][C:6]1[C:7]2[CH:8]=[N:9][CH:10]=[CH:11][C:12]=2[N:13]([CH2:14][CH2:15][O:16][Si:17]([CH:18]([CH3:19])[CH3:20])([CH:21]([CH3:22])[CH3:23])[CH:24]([CH3:26])[CH3:25])[C:5]=1[C:3]([NH2:43])=[O:2]

参加物

7

反応物 5

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595965243-(2-Fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

生成物 1

HCID 595964823-(2-Fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid amide収率 80%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
65 °C

実験手順

To a suspension of 3-(2-fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester (132 mg, 0.22 mmol) in ethanol (3 mL) was added a 1M aqueous solution of sodium hydroxide (0.23 mL, 0.23 mmol). The reaction mixture was heated at 65° C., stirred for 1 hour, cooled to room temperature, concentrated and azeotroped with toluene. The residue was suspended in DMF and ammonium chloride (24 mg, 0.44 mmol), diisopropylethylamine (0.15 mL, 0.88 mmol) then HATU (167 mg, 0.44 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours before being partitioned between ethyl acetate and water. The organic layer was isolated and washed with water then a saturated solution of sodium hydrogencarbonate and then brine, dried (Na2SO4), filtered and evaporated to give the title compound as a yellow solid (105 mg, 80%). LCMS (method B): RT=3.03 min, M+H+=597.

後処理

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. customazeotroped with toluene
  4. stirringThe reaction mixture was stirred at room temperature for 16 hours
  5. custombefore being partitioned between ethyl acetate and water
  6. customThe organic layer was isolated
  7. washwashed with water
  8. dry with materiala saturated solution of sodium hydrogencarbonate and then brine, dried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated

出典と根拠

ORDレコード
ord-7e1645496f9a41099c78b0d7f6cfd6af
出典データセット
uspto-grants-2010_12
特許番号
US07855216B2

反応ノート

読み込み中…