4-{[7-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carbonyl]-aminooxy}-piperidine-1-carboxylic acid tert-butyl ester → 7-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid (piperidin-4-yloxy)-amide

HRID 450127Notes

Reaction equation

HRID 450127 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][NH:15][C:16]([C:18]2[CH:19]=[C:20]3[CH:25]=[CH:24][N:23]=[CH:22][N:21]3[C:26]=2[NH:27][C:28]2[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:29]=2[F:35])=[O:17])[CH2:10][CH2:9]1)=O)(C)(C)C>Cl.O1CCOCC1>[NH:8]1[CH2:13][CH2:12][CH:11]([O:14][NH:15][C:16]([C:18]2[CH:19]=[C:20]3[CH:25]=[CH:24][N:23]=[CH:22][N:21]3[C:26]=2[NH:27][C:28]2[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:29]=2[F:35])=[O:17])[CH2:10][CH2:9]1

Participants

4

Reactant 1

HCID 866542874-{[7-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carbonyl]-aminooxy}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 441333337-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid (piperidin-4-yloxy)-amideYield 25%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

4-{[7-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carbonyl]-aminooxy}-piperidine-1-carboxylic acid tert-butyl ester (180 mg, 0.30 mmol) was dissolved in hydrochloric acid in dioxane (1 mL, 4M). The reaction was stirred at room temperature for 30 minutes then concentrated in vacuo. The resultant residue was subject to reverse phase HPLC (gradient 10-60% acetonitrile/water 0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm). The product was dissolved in ethyl acetate (5 mL), washed with aqueous saturated sodium bicarbonate solution (10 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo to yield the title compound as a yellow solid (37 mg, 25%). 1H NMR (DMSO-d6): 8.73 (1H, s), 7.92 (1H, s), 7.49 (1H, dd, J=10.98, 1.92 Hz), 7.41-7.38 (2H, m), 7.16-7.13 (1H, m), 6.72 (1H, d, J=0.92 Hz), 5.93 (1H, t, J=8.84 Hz), 3.72-3.62 (1H, m), 2.87 (2H, dt, J=12.72, 4.49 Hz), 2.41-2.31 (2H, m), 1.67 (2H, dt, J=12.84, 4.01 Hz), 1.32-1.21 (2H, m). LCMS (Method A): RT=6.17 min, M+H+=496.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe product was dissolved in ethyl acetate (5 mL)
  3. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  4. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
  5. washThe combined organic fractions were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a017803878e447fe828ee73414bf76aa
Source dataset
uspto-grants-2013_07
Patent number
US08486963B2

Reaction notes

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