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

HRID 2264964ノート

反応式

HRID 2264964 の反応式
CO[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:4].[OH-].[Na+].[CH:38]([O:40][CH2:41][CH2:42][O:43][NH2:44])=[CH2:39].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(O)C.C1COCC1>[CH:38]([O:40][CH2:41][CH2:42][O:43][NH:44][C:3]([C:5]1[N:13]([CH2:14][CH2:15][O:16][Si:17]([CH:18]([CH3:19])[CH3:20])([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:22])[CH3:23])[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:4])=[CH2:39]

参加物

9

反応物 6

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 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 595966633-(2-fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran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 (90 mg, 0.15 mmol) in ethanol (2 mL) was added a 1M aqueous solution of sodium hydroxide (0.15 mL, 0.15 mmol). The reaction mixture was heated at 65° C., stirred for 1 hour, cooled to room temperature, concentrated and azeotroped with toluene. The resultant residue was suspended in THF to which O-(2-vinyloxy-ethyl)-hydroxylamine (31 mg, 0.30 mmol), EDCI (37 mg, 0.19 mmol), HOBt (30 mg, 0.22 mmol) and DIPEA (105 μl, 0.60 mmol) were added. The reaction mixture was stirred at room temperature for 16 h then concentrated to give a residue which was purified by flash chromatography (Si-PPC, cyclohexane:EtOAc, gradient 100:0 to 0:100). The title compound was obtained as a yellow solid (58 mg, 57%). LCMS (method B): RT=3.24 min, M+H+=683.

後処理

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. customazeotroped with toluene
  4. additionwere added
  5. stirringThe reaction mixture was stirred at room temperature for 16 h
  6. concentrationthen concentrated
  7. customto give a residue which
  8. customwas purified by flash chromatography (Si-PPC, cyclohexane:EtOAc, gradient 100:0 to 0:100)

出典と根拠

ORDレコード
ord-7f770d92c72b4e2aaed5969809ff760d
出典データセット
uspto-grants-2010_12
特許番号
US07855216B2

反応ノート

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