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

HRID 246268노트

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HRID 246268 반응식
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[N:21]=[C:22]4[C:28]([CH:29]=[O:30])=[CH:27][N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:23]4=[N:24][CH:25]=3)=[N:7][N:8]2[CH2:11][C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][CH:3]=1.S(=O)(=O)([OH:41])N.Cl([O-])=O.[Na+].P([O-])(O)(O)=O.[K+]>C1COCC1.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[N:21]=[C:22]4[C:28]([C:29]([OH:41])=[O:30])=[CH:27][N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:23]4=[N:24][CH:25]=3)=[N:7][N:8]2[CH2:11][C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 5987Sulfamic AcidHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 866779702-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

생성물 1

HCID 712800952-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid수율 95.3%

시약·촉매·용매 2

HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

In a 50 ml round-bottomed flask, 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (265 mg, 0.49 mmol) was dissolved in THF (10 ml) and water (2 ml). The yellow solution was cooled to 0° C. and sulfamic acid (287 mg, 2.95 mmol) was added. Then, a solution of sodium chlorite (80%, 76 mg, 0.67 mmol) and potassium dihydrogen phosphate (803 mg, 5.9 mmol) in water (6 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 2 h. The reaction mixture 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/ethyl acetate to afford 259 mg (95%) of 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid as a light yellow powder.

후처리

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. additionThe reaction mixture 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/ethyl acetate

출처 및 근거

ORD 기록
ord-dddae2411ad44dc9ba975eaf6c427c28
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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