Hydrochloric Acid → 1-Cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[32-c]pyridine-2-carboxylic acid (2,3-dihydroxy-propoxy)-amide

HRID 2264977Notes

Reaction equation

HRID 2264977 reaction equation
CC1(C)[O:6][CH:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[N:20]([CH:21]3[CH2:23][CH2:22]3)[C:19]3[CH:18]=[CH:17][N:16]=[CH:15][C:14]=3[C:13]=2[NH:24][C:25]2[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=2[F:32])=[O:11])[CH2:4][O:3]1.Cl>CO.O1CCOCC1>[OH:6][CH:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10]([C:12]1[N:20]([CH:21]2[CH2:22][CH2:23]2)[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:13]=1[NH:24][C:25]1[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=1[F:32])=[O:11]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 595965981-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Product 1

HCID 595966111-Cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[32-c]pyridine-2-carboxylic acid (2,3-dihydroxy-propoxy)-amideYield 5.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To 1-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]-pyridine-2-carboxylic acid (2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (65.0 mg, 0.12 mmol) in anhydrous methanol (1.8 mL) was added 4 M Hydrogen chloride in 1,4-Dioxane (1.0 mL), and the reaction mixture was stirred at ambient temperature for 17 h. The solvent was removed in vacuo and the residue was redissolved in acetonitrile (2.0 mL) and loaded onto a Phenomenex Strata-X cartridge (5 g). The cartridge was washed with water (10 mL) and methanol (15 ml). The desired product was then eluted using 2M ammonia in MeOH. Methanol was removed in vacuo to give a brown oil, which was purified by HPLC to obtain 3.3 mg (5.5%) of the desired product as the TFA salt. 1H-NMR (500 MHz, MeOD.) δ ppm 8.96 (s, 1H), 8.45 (d, J=6.81 Hz, 1H), 8.18 (d, J=6.77 Hz, 1H), 7.48 (dd, J=10.76 Hz, 1H), 7.28 (d, J=8.50 Hz, 1H), 6.56 (t, J=9.6, 1H), 4.01-3.86 (m, 1H), 3.85-3.75 (m, 2H), 3.75-3.64 (m, 1H), 3.63-3.47 (m, 2H), 1.34-1.29 (m, 2H), 1.09-1.04 (m, 2H); LC-MS (method D): [M+H]+=527.0, RT=3.33 min.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was redissolved in acetonitrile (2.0 mL)
  3. washThe cartridge was washed with water (10 mL) and methanol (15 ml)
  4. washThe desired product was then eluted
  5. customMethanol was removed in vacuo
  6. customto give a brown oil, which
  7. customwas purified by HPLC

Sources & evidence

ORD record
ord-961a0b420f554054842d6d8ba9d0484c
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

Loading…