Sodium Hydroxide → 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

HRID 2264958ノート

反応式

HRID 2264958 の反応式
C(O[C:4]([C:6]1[N:14]([CH3:15])[C:13]2[CH:12]=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=1[F:24])=[O:5])C.[OH-].[Na+].[CH3:27][C:28]1([CH3:36])[O:32][C@@H:31]([CH2:33][O:34][NH2:35])[CH2:30][O:29]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C1COCC1.C(O)C>[CH3:27][C:28]1([CH3:36])[O:32][C@@H:31]([CH2:33][O:34][NH:35][C:4]([C:6]2[N:14]([CH3:15])[C:13]3[CH:12]=[CH:11][N:10]=[CH:9][C:8]=3[C:7]=2[NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[O:5])[CH2:30][O:29]1

参加物

9

反応物 6

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11298047(R)-O-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)hydroxylamineHCID 595965873-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

生成物 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収率 65%

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

A mixture of 3-(2-fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (90 mg, 0.21 mmol), 1N aqueous NaOH solution (0.22 ml, 0.22 mmol) and ethanol (3 ml) were heated at 65° C. for 2.5 hours. The reaction mixture was concentrated and then azeotroped with toluene (2×5 ml) to give a solid residue. The solid residue was dissolved in anhydrous THF (5 ml) and O—((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)hydroxylamine (49 mg, 0.41 mmol), EDCI (49 mg, 0.26 mmol), HOBt (39 mg, 0.29 mmol) and DIPEA (109 μl, 0.62 mmol) were added. After stirring for 19 hours the solvent was evaporated and the residue was partitioned between ethyl acetate (30 ml) and water (20 ml). The organic layer was isolated, dried over sodium sulphate then filtered and evaporated to give a yellow oil. The oil was purified by flash chromatography (Si-PPC, pentane:ethyl acetate, gradient 50:50 to 0:100) to afford the title compound as a yellow solid (71 mg, 65%). LCMS (method B): RT=2.87 min, M+H+=542.

後処理

  1. concentrationThe reaction mixture was concentrated
  2. customazeotroped with toluene (2×5 ml)
  3. customto give a solid residue
  4. customwas evaporated
  5. customthe residue was partitioned between ethyl acetate (30 ml) and water (20 ml)
  6. customThe organic layer was isolated
  7. dry with materialdried over sodium sulphate
  8. filtrationthen filtered
  9. customevaporated
  10. customto give a yellow oil
  11. customThe oil was purified by flash chromatography (Si-PPC, pentane:ethyl acetate, gradient 50:50 to 0:100)

出典と根拠

ORDレコード
ord-74c5b384a28c4f61bf2510874f6fd832
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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