Sulfamic Acid → 2-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

HRID 246285ノート

反応式

HRID 246285 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([F:23])[CH:21]=3)[C:16]([C:24]3[N:25]=[C:26]4[C:32]([CH:33]=[O:34])=[CH:31][N:30]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C:27]4=[N:28][CH:29]=3)=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(=O)(=O)([OH:45])N.Cl([O-])=O.[Na+].P([O-])(O)(O)=O.[K+]>C1COCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([F:23])[CH:21]=3)[C:16]([C:24]3[N:25]=[C:26]4[C:32]([C:33]([OH:45])=[O:34])=[CH:31][N:30]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C:27]4=[N:28][CH:29]=3)=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 5987Sulfamic AcidHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 866779724-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 712802552-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid収率 90.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

In a 50 ml round-bottomed flask, 4-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (190 mg, 0.32 mmol) was dissolved in THF (7 ml) and water (1.4 ml). The light yellow solution was cooled to 0° C. and sulfamic acid (186 mg, 1.92 mmol) was added. Then, a solution of sodium chlorite (80%, 50 mg, 0.44 mmol) and potassium dihydrogen phosphate (522 mg, 3.83 mmol) in water (4.2 ml) was added dropwise via pipette. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 1.5 h. The reaction was diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was triturated with hexanes to afford 176 mg (90%) of 2-[1-(1-tertbutoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid as a light yellow powder.

後処理

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. additionThe reaction was diluted with water
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was triturated with hexanes

出典と根拠

ORDレコード
ord-6bc80cb6446e488eaaa8c43e241a7bc6
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…