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

HRID 450129Notes

Reaction equation

HRID 450129 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[CH:13]=[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]([S:28][CH3:29])=[CH:24][C:23]=2[F:30])=[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[CH:13]=[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]([S:28][CH3:29])=[CH:24][C:23]=1[F:30])=[O:11]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 867619437-(2-Fluoro-4-methylsulfanyl-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

Product 1

HCID 441333347-(2-Fluoro-4-methylsulfanyl-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid ((R)-2,3-dihydroxy-propoxy)-amideYield 45%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-(2-fluoro-4-methylsulfanyl-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid ((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide (246 mg, 0.56 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% DCM in methanol) to yield a light brown solid. The solid was triturated with acetonitrile (3 mL) to yield the title compound as a beige solid (100 mg, 45%). 1H NMR (DMSO-d6): 11.38 (1H, s), 8.64 (1H, t, J=1.05 Hz), 7.86 (1H, s), 7.41-7.39 (2H, m), 7.15 (1H, dd, J=12.09, 2.09 Hz), 6.82-6.79 (1H, m), 6.73 (1H, s), 6.06 (1H, t, J=8.82 Hz), 4.82 (1H, s), 4.53 (1H, s), 3.80 (1H, dd, J=9.68, 3.51 Hz), 3.67-3.57 (2H, m), 3.31-3.24 (2H, m). (SMe coincident with solvent). LCMS (Method A): RT=7.14 min, M+H+=407.

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-f8dd75653ebf479488191152ee55e126
Source dataset
uspto-grants-2013_07
Patent number
US08486963B2

Reaction notes

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