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

HRID 2264962Notes

Reaction equation

HRID 2264962 reaction equation
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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-7e1645496f9a41099c78b0d7f6cfd6af
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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