t-Butylammonium fluoride → 3-(2-Fluoro-4-iodo-phenylamino)-1-(2-hydroxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-hydroxy-ethoxy)-amide

HRID 2264965Notes

Reaction equation

HRID 2264965 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[N:18]([CH2:19][CH2:20][O:21][Si](C(C)C)(C(C)C)C(C)C)[C:17]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[C:11]=1[NH:32][C:33]1[CH:38]=[CH:37][C:36]([I:39])=[CH:35][C:34]=1[F:40])=[O:9])=C.[F-].C([NH3+])(C)(C)C>C1COCC1>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[N:18]([CH2:19][CH2:20][OH:21])[C:17]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[C:11]=1[NH:32][C:33]1[CH:38]=[CH:37][C:36]([I:39])=[CH:35][C:34]=1[F:40])=[O:9]

Participants

4

Reactant 2

HCID 21866379t-Butylammonium fluorideHCID 595966633-(2-fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide

Product 1

HCID 595966243-(2-Fluoro-4-iodo-phenylamino)-1-(2-hydroxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-hydroxy-ethoxy)-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(2-fluoro-4-iodo-phenylamino)-1-(2-triisopropylsilanyloxy-ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide (58 mg, 0.085 mmol) in THF (2 mL) was added a 1M solution of tert-butylammonium fluoride in THF (0.1 mL, 0.1 mmol). The reaction mixture was stirred at room temperature for 1 hour and passed through a 5 g SCX-2 cartridge eluting with MeOH then 2M solution of ammonia in MeOH. The appropriate fractions were combined and concentrated to give a residue that was purified by flash chromatography (Si-PPC, MeOH:DCM, gradient 0:100 to 30:70). The title compound was obtained as a yellow solid (16 mg, 38%). LCMS (method A): RT=5.13 min, M+H+=501. 1H NMR (CDOD) 3.70 (2H, m), 3.90 (2H, t, J=5.3 Hz), 3.94 (2H, m), 4.60 (2H, t, J=5.3 Hz), 6.42 (1H, t, J=8.9 Hz), 7.2 (1H, m), 7.43 (1H, dd, J=10.9, 1.9 Hz), 7.60 (1H, dd, J=6.2, 0.9 Hz), 8.26 (1H, d, J=6.2 Hz), 8.58 (1H, d, J=0.9 Hz).

Workup

  1. washeluting with MeOH
  2. concentrationconcentrated
  3. customto give a residue that
  4. customwas purified by flash chromatography (Si-PPC, MeOH:DCM, gradient 0:100 to 30:70)

Sources & evidence

ORD record
ord-7fd3717f0f6b4db486915e19ab34ceae
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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