Sulfamic Acid → 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

HRID 246378

反応式

HRID 246378 の反応式
[F:1][CH:2]([F:33])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[N:8]=[C:7]2[C:14]1[N:15]=[C:16]2[C:22]([CH:23]=[O:24])=[CH:21][N:20]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:17]2=[N:18][CH:19]=1.S(=O)(=O)([OH:36])N.Cl([O-])=O.[Na+].OP([O-])(O)=O.[K+]>O1CCOCC1.O>[F:33][CH:2]([F:1])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[N:8]=[C:7]2[C:14]1[N:15]=[C:16]2[C:22]([C:23]([OH:36])=[O:24])=[CH:21][N:20]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:30])([CH3:32])[CH3:31])[C:17]2=[N:18][CH:19]=1

参加物

7

反応物 4

HCID 5987Sulfamic Acid2 回HCID 516951Monobasic potassium phosphate2 回HCID 23668197Sodium Chlorite2 回HCID 866779762-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

生成物 1

HCID 712805312-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid収率 57%

試薬・触媒・溶媒 2

HCID 962Water溶媒4 回HCID 312751,4-Dioxane溶媒

反応条件

温度
25 °C

実験手順

To a solution of 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (217 mg, 458 μmol) in dioxane (6.5 mL) and water (2 mL) at 0° C. was added sulfamic acid (267 mg, 2.75 mmol), followed by drop-wise addition of a solution of sodium chlorite (67.3 mg, 596 μmol) and KH2PO4 (748 mg, 5.5 mmol) in water (4.5 mL) via dropping funnel over 15 min. The ice bath was removed and the light yellow suspension was stirred at 25° C. for 18 h. THF (6.5 mL) added to the yellow suspension and reaction continued at 25° C. for 2 h, then sulfamic acid (267 mg, 2.75 mmol) was added followed by dropwise addition of sodium chlorite (67.3 mg, 596 μmol) and KH2PO4 (748 mg, 5.5 mmol) in 5 mL of water. After 2 h the mixture was diluted with water (20 mL) and extracted with dichloromethane (3×30 mL). The combined organic layers were dried (MgSO4) and evaporated. The light yellow solid residue was dissolved in dichloromethane/MeOH and dichloromethane evaporated to promote solid formation, the solid separated by filtration, rinsed with MeOH and hexanes then dried to give 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (127 mg, 259 μmol, 57%) as a light yellow solid. MS (M+H)+=490; 1H NMR (DMSO-d6) δ: 12.57 (br. s., 1H), 9.12 (s, 1H), 8.69 (s, 1H), 8.65 (d, J=2.3 Hz, 1H), 7.80 (d, J=9.1 Hz, 1H), 7.35 (dd, J=8.9, 2.5 Hz, 1H), 7.20 (t, J=74.8 Hz, 1H), 5.71 (s, 2H), 4.18 (s, 3H), 3.58 (t, J=7.9 Hz, 2H), 0.84 (t, J=7.9 Hz, 2H), −0.21-−0.01 (s, 9H).

後処理

  1. customover 15 min
  2. customThe ice bath was removed
  3. additionTHF (6.5 mL) added to the yellow suspension and reaction
  4. waitcontinued at 25° C. for 2 h
  5. extractionextracted with dichloromethane (3×30 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. customevaporated
  8. dissolutionThe light yellow solid residue was dissolved in dichloromethane/MeOH
  9. customdichloromethane evaporated
  10. customthe solid separated by filtration
  11. washrinsed with MeOH and hexanes
  12. customthen dried

出典と根拠

ORDレコード
ord-b2ffef7ca09649bdb64e56dfba1ac544
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

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