Tetrabutylammonium Fluoride → 3-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ((S)-2-hydroxy-propoxy)-amide

HRID 2264967Notes

Reaction equation

CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Si]([O:26][C@@H:27]([CH3:52])[CH2:28][O:29][NH:30][C:31]([C:33]1[N:41]([CH3:42])[C:40]2[CH:39]=[CH:38][N:37]=[CH:36][C:35]=2[C:34]=1[NH:43][C:44]1[CH:49]=[CH:48][C:47]([I:50])=[CH:46][C:45]=1[F:51])=[O:32])(C(C)(C)C)(C)C>C1COCC1>[OH:26][C@@H:27]([CH3:52])[CH2:28][O:29][NH:30][C:31]([C:33]1[N:41]([CH3:42])[C:40]2[CH:39]=[CH:38][N:37]=[CH:36][C:35]=2[C:34]=1[NH:43][C:44]1[CH:49]=[CH:48][C:47]([I:50])=[CH:46][C:45]=1[F:51])=[O:32]

Participants

Conditions

Temperature: 45 °C

Procedure

TBAF (1.71 ml, 1N solution in THF, 1.71 mmol) was added to a solution of 3-(2-fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid [(S)-2-(tert-butyldimethylsilanyloxy)-propoxy]-amide (171 mg, 0.29 mmol) in THF (3 ml) and the reaction heated at 45° C. for 4.5 hours. The reaction was concentrated in vacuo and the resultant residue purified by flash chromatography (SiO2, gradient 0-10% methanol in dichloromethane) to yield the title compound as a yellow solid (35 mg, 25%). 1H NMR (DMSO-D6, 400 MHz) 8.54 (1H, s), 8.27 (1H, d, J=5.7 Hz), 7.56-7.50 (2H, m), 7.48 (1H, dd, J=11.0, 2.1 Hz), 7.16-7.13 (1H, m), 6.18 (1H, t, J=8.9 Hz), 3.81 (3H, s), 3.74-3.67 (1H, m), 3.57-3.55 (2H, m), 0.95 (3H, d, J=5.99 Hz). LCMS (method A): RT=5.82 min, M+H+=485.

Workup

concentrationThe reaction was concentrated in vacuo
customthe resultant residue purified by flash chromatography (SiO2, gradient 0-10% methanol in dichloromethane)

Sources & evidence

ORD record: ord-85e779b4614247e89113b310182fc8bd
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07855216B2

Reaction notes

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