2-Methoxyethylamine → 1-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid[6-(2-methoxy-ethylsulfamoyl)-pyridin-3-ylmethyl]-amide

HRID 1361128ノート

反応式

HRID 1361128 の反応式
COC(=O)CC[S:6]([C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH:16][C:17]([C:19]2[C:20]3[CH:27]=[N:26][N:25]([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[C:21]=3[CH:22]=[N:23][CH:24]=2)=[O:18])=[CH:11][N:10]=1)(=[O:8])=[O:7].[O-]CC.[Na+].ClN1C(=O)CCC1=O.[CH3:48][O:49][CH2:50][CH2:51][NH2:52]>C1COCC1.C(O)C.[Cl-].[NH4+].CCOC(C)=O>[CH3:48][O:49][CH2:50][CH2:51][NH:52][S:6]([C:9]1[N:10]=[CH:11][C:12]([CH2:15][NH:16][C:17]([C:19]2[C:20]3[CH:27]=[N:26][N:25]([C:28]4[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=4)[C:21]=3[CH:22]=[N:23][CH:24]=2)=[O:18])=[CH:13][CH:14]=1)(=[O:7])=[O:8]

参加物

9

反応物 4

HCID 80182-MethoxyethylamineHCID 31398ChlorosuccinimideHCID 2723922Sodium ethoxideHCID 592783133-[5-({[1-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]-amino}-methyl)-pyridine-2-sulfonyl]-propionic acid methyl ester

生成物 1

HCID 592783991-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid[6-(2-methoxy-ethylsulfamoyl)-pyridin-3-ylmethyl]-amide

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒HCID 25517Ammonium Chloride溶媒

実験手順

To a solution of 3-[5-({[1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]-amino}-methyl)-pyridine-2-sulfonyl]-propionic acid methyl ester (100 mg, 0.2 mmol) in THF (5 mL) was added a freshly prepared 8% solution of sodium ethoxide (200 μL, 0.2 mmol) in ethanol. The mixture was stirred for 15 minutes and was monitored for the disappearance of starting material by TLC (EtOAc). The mixture was then concentrated to dryness under a stream of nitrogen. The mixture was again diluted with THF and then N-chlorosuccinimide (55 mg, 0.41 mmol) was added. After 15 minutes, 2-methoxyethylamine (0.100 mL, 1.15 mmol) was added in one portion. After 15 minutes, the mixture was diluted with saturated ammonium chloride and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (2×10 mL), dried over magnesium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography eluting with methanol-EtOAc (0:100, then 0.5:99.5, then 1:99, then 2:98). The material from the column was purified a second time by using preparative silica gel TLC eluting with methanol-EtOAc (1:9). The material from the plate was triturated with EtOAc-ether-hexanes to afford the title compound.

後処理

  1. concentrationThe mixture was then concentrated to dryness under a stream of nitrogen
  2. additionThe mixture was again diluted with THF
  3. waitAfter 15 minutes
  4. waitAfter 15 minutes
  5. extractionextracted with EtOAc (3×10 mL)
  6. washThe combined organic layers were washed with brine (2×10 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by silica gel chromatography
  11. washeluting with methanol-EtOAc (0:100
  12. customThe material from the column was purified a second time
  13. washeluting with methanol-EtOAc (1:9)
  14. customThe material from the plate was triturated with EtOAc-ether-hexanes

出典と根拠

ORDレコード
ord-a4e2d22a04e64d0c88187356fda8e521
出典データセット
uspto-grants-2011_02
特許番号
US07879873B2

反応ノート

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