Hydrochloric Acid → 1-(2,3-Dihydroxy-propyl)-cyclopropanesulfonic acid [7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-1,2,3,5-tetrahydro-imidazo[1,2-a]pyridin-8-yl]-amide

HRID 1259378Notes

Reaction equation

HRID 1259378 reaction equation
Cl.C(OC([N:9]1[C:13]2=[C:14]([NH:29][S:30]([C:33]3([CH2:36][CH:37]([OH:40])[CH2:38][OH:39])[CH2:35][CH2:34]3)(=[O:32])=[O:31])[C:15]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=3[F:28])=[C:16]([CH3:19])[C:17](=[O:18])[N:12]2[CH2:11][CH2:10]1)=O)(C)(C)C.CO>C1COCC1.C(Cl)(Cl)Cl>[F:28][C:22]1[CH:23]=[C:24]([I:27])[CH:25]=[CH:26][C:21]=1[NH:20][C:15]1[C:14]([NH:29][S:30]([C:33]2([CH2:36][CH:37]([OH:40])[CH2:38][OH:39])[CH2:34][CH2:35]2)(=[O:31])=[O:32])=[C:13]2[NH:9][CH2:10][CH2:11][N:12]2[C:17](=[O:18])[C:16]=1[CH3:19]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 671938308-[1-(2,3-Dihydroxy-propyl)-cyclopropanesulfonylamino]-7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-2,3-dihydro-5H-imidazo[1,2-a]pyridine-1-carboxylic acid tert-butyl ester

Product 1

HCID 529347851-(2,3-Dihydroxy-propyl)-cyclopropanesulfonic acid [7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-1,2,3,5-tetrahydro-imidazo[1,2-a]pyridin-8-yl]-amideYield 14.7%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

Concentrated HCl (3 mL) was added to a stirred solution of 8-[1-(2,3-dihydroxy-propyl)-cyclopropanesulfonylamino]-7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-2,3-dihydro-5H-imidazo[1,2-a]pyridine-1-carboxylic acid tert-butyl ester (80 mg) in THF (5 mL). The resulting mixture was stirred at 40° C. for 2 hours. The reaction was monitored by TLC (15% MeOH in CHCl3). The reaction mixture was concentrated and partitioned between ethylacetate and water. The organic layer was washed with saturated NaHCO3 solution and concentrated to afford the crude product. Purification by column chromatography on silica gel (5% methanol in CHCl3), followed by preparative HPLC afforded 10 mg of the product (14.7% yield)

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between ethylacetate and water
  3. washThe organic layer was washed with saturated NaHCO3 solution
  4. concentrationconcentrated
  5. customto afford the crude product
  6. customPurification by column chromatography on silica gel (5% methanol in CHCl3)

Sources & evidence

ORD record
ord-4dfe87bb825c42e9956d5e4c40665051
Source dataset
uspto-grants-2013_06
Patent number
US08466289B2

Reaction notes

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