Sodium Hydroxide → 3-(2-Fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid amide

HRID 2264962노트

반응식

HRID 2264962 반응식
C[O:2][C:3]([C:5]1[N:13]([CH2:14][CH2:15][O:16][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])[C:12]2[CH:11]=[CH:10][N:9]=[CH:8][C:7]=2[C:6]=1[NH:27][C:28]1[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:29]=1[F:35])=O.[OH-].[Na+].[Cl-].[NH4+].C([N:43](C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(O)C>[F:35][C:29]1[CH:30]=[C:31]([I:34])[CH:32]=[CH:33][C:28]=1[NH:27][C:6]1[C:7]2[CH:8]=[N:9][CH:10]=[CH:11][C:12]=2[N:13]([CH2:14][CH2:15][O:16][Si:17]([CH:18]([CH3:19])[CH3:20])([CH:21]([CH3:22])[CH3:23])[CH:24]([CH3:26])[CH3:25])[C:5]=1[C:3]([NH2:43])=[O:2]

참가 물질

7

반응물 5

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595965243-(2-Fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester

생성물 1

HCID 595964823-(2-Fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid amide수율 80%

시약·촉매·용매 1

HCID 702Ethanol용매

반응 조건

온도
65 °C

실험 절차

To a suspension of 3-(2-fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid methyl ester (132 mg, 0.22 mmol) in ethanol (3 mL) was added a 1M aqueous solution of sodium hydroxide (0.23 mL, 0.23 mmol). The reaction mixture was heated at 65° C., stirred for 1 hour, cooled to room temperature, concentrated and azeotroped with toluene. The residue was suspended in DMF and ammonium chloride (24 mg, 0.44 mmol), diisopropylethylamine (0.15 mL, 0.88 mmol) then HATU (167 mg, 0.44 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours before being partitioned between ethyl acetate and water. The organic layer was isolated and washed with water then a saturated solution of sodium hydrogencarbonate and then brine, dried (Na2SO4), filtered and evaporated to give the title compound as a yellow solid (105 mg, 80%). LCMS (method B): RT=3.03 min, M+H+=597.

후처리

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. customazeotroped with toluene
  4. stirringThe reaction mixture was stirred at room temperature for 16 hours
  5. custombefore being partitioned between ethyl acetate and water
  6. customThe organic layer was isolated
  7. washwashed with water
  8. dry with materiala saturated solution of sodium hydrogencarbonate and then brine, dried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated

출처 및 근거

ORD 기록
ord-7e1645496f9a41099c78b0d7f6cfd6af
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07855216B2

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