Hydrochloric Acid → 5-Chloro-7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amide

HRID 450133Notes

Reaction equation

HRID 450133 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[C:13]([Cl:30])=[C:14]3[CH:19]=[CH:18][N:17]=[CH:16][N:15]3[C:20]=2[NH:21][C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[F:29])=[O:11])[CH2:4][O:3]1.Cl.O1CCOCC1>CO.C(OCC)(=O)C>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10]([C:12]1[C:13]([Cl:30])=[C:14]2[CH:19]=[CH:18][N:17]=[CH:16][N:15]2[C:20]=1[NH:21][C:22]1[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=1[F:29])=[O:11]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 867619445-Chloro-7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Product 1

HCID 441333365-Chloro-7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-chloro-7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (57 mg, 0.1 mmol) in methanol (1 mL) was added a solution of hydrochloric acid in dioxane (1 mL, 4M, 4 mmol). The reaction was stirred at room temperature for 1 hour then diluted with ethyl acetate (5 mL), washed with saturated aqueous 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. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-10% methanol in DCM) to yield a light brown solid. The solid was triturated with acetonitrile (3 mL) to yield the title compound as an off white solid (13 mg, 45%). 1H NMR (CH3 OH-d4): 8.74 (1H, d, J=1.57 Hz), 7.49 (1H, d, J=6.61 Hz), 7.42 (1H, dd, J=10.78, 1.91 Hz), 7.38 (1H, dd, J=6.61, 1.58 Hz), 7.21 (1H, ddd, J=8.48, 1.90, 1.11 Hz), 6.14 (1H, t, J=8.76 Hz), 3.89-3.80 (1H, m), 3.79-3.71 (2H, m), 3.56-3.42 (2H, m). LCMS (Method A): RT=7.70 min, M+H+=521.

Workup

  1. washwashed with saturated aqueous sodium bicarbonate solution (10 mL)
  2. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
  3. washThe combined organic fractions were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto yield a light brown solid
  7. customThe solid was triturated with acetonitrile (3 mL)

Sources & evidence

ORD record
ord-cb7943c811fa44f9a332afedd0d2c2dd
Source dataset
uspto-grants-2013_07
Patent number
US08486963B2

Reaction notes

Loading…