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 2264959노트

반응식

HRID 2264959 반응식
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]

참가 물질

3

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-1da9062c7d384a16938083e5da75ecf0
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07855216B2

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