Hydrochloric Acid → 7-(2-Fluoro-4-methylsulfanyl-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid (2-hydroxy-ethoxy)-amide

HRID 450131Notes

Reaction equation

HRID 450131 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]2[C:18]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([S:26][CH3:27])=[CH:22][C:21]=1[F:28])=[O:9])=C.Cl>>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]2[C:18]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([S:26][CH3:27])=[CH:22][C:21]=1[F:28])=[O:9]

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 866542887-(2-Fluoro-4-methylsulfanyl-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide

Product 1

HCID 441333357-(2-Fluoro-4-methylsulfanyl-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid (2-hydroxy-ethoxy)-amideYield 56%

Procedure

To a solution of 7-(2-fluoro-4-methylsulfanyl-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide in IMS was added aqueous hydrochloric acid (4 N, 0.5 mL). The reaction was stirred at room temperature for 1 hour then concentrated in vacuo. The resultant residue 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 (2×5 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 the title compound as an off-white solid (73 mg, 56%). 1H NMR (DMSO-d6): 11.31 (1H, s), 8.65 (1H, s), 7.85 (1H, s), 7.42-7.37 (2H, m), 7.15 (1H, dd, J=12.10, 2.09 Hz), 6.82-6.79 (1H, m), 6.73 (1H, s), 6.06 (1H, t, J=8.82 Hz), 4.66 (1H, s), 3.75 (2H, dd, J=5.34, 4.47 Hz), 3.46 (2H, t, J=4.82 Hz), 2.36 (3H, s). LCMS (Method A): RT=7.35 min, M+H+=377.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe resultant residue 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 (2×5 mL)
  5. washThe combined organic fractions were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-054fe6d5a807451d937aef9c36b5959a
Source dataset
uspto-grants-2013_07
Patent number
US08486963B2

Reaction notes

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