3-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide → 3-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amide

HRID 2264959ノート

反応式

HRID 2264959 の反応式
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[N:20]([CH3:21])[C:19]3[CH:18]=[CH:17][N:16]=[CH:15][C:14]=3[C:13]=2[NH:22][C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=2[F:30])=[O:11])[CH2:4][O:3]1>CO>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10]([C:12]1[N:20]([CH3:21])[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:13]=1[NH:22][C:23]1[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=1[F:30])=[O:11]

参加物

3

反応物 1

HCID 595965023-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

生成物 1

HCID 249483223-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amide収率 18.5%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

3-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (71 mg, 0.13 mmol) was dissolved in methanol (0.5 ml) and loaded onto an Isolute® SCX-2 cartridge (5 g). The cartridge was then washed with methanol (15 ml) and the desired product was subsequently eluted using 2M NH3 in MeOH. The eluant was collected and concentrated to give a residue. The residue was purified by flash chromatography (Si-PPC, dichloromethane:MeOH, gradient 100:0 to 90:10) followed by reversed phase HPLC (Phenomenex Luna 5 phenyl/hexyl, 0.1% TFA in water on a gradient of acetonitrile 100:0 to 40:60) to afford the title compound as a white solid (12 mg, 15%). LCMS (method A): RT=4.83 min, M+H+=501. 1H NMR (d4-MeOH, 400 MHz) 8.61 (s, 1H), 8.30 (d, J=6.0 Hz, 1H), 7.59 (d, J=6.0 Hz, 1H), 7.44 (dd, J=11.0 Hz, 1.8 Hz, 1H), 7.18-7.23 (m, 1H), 6.37 (dd, J=9.0 Hz, 9.0 Hz, 1H), 3.99 (s, 3H), 3.89-3.95 (m, 1H), 3.77-3.86 (m, 2H), 3.47-3.59 (m, 2H).

後処理

  1. washThe cartridge was then washed with methanol (15 ml)
  2. washthe desired product was subsequently eluted
  3. customThe eluant was collected
  4. concentrationconcentrated
  5. customto give a residue
  6. customThe residue was purified by flash chromatography (Si-PPC, dichloromethane:MeOH, gradient 100:0 to 90:10)

出典と根拠

ORDレコード
ord-1da9062c7d384a16938083e5da75ecf0
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…