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 2264964노트

반응식

HRID 2264964 반응식
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]

참가 물질

9

반응물 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

생성물 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

시약·촉매·용매 2

HCID 702Ethanol용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
65 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-7f770d92c72b4e2aaed5969809ff760d
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07855216B2

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