Methanol → 3-Hydroxy-cyclobutanesulfonic acid [7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridin-8-yl]-amide

HRID 1259432Notes

Reaction equation

HRID 1259432 reaction equation
B(Cl)(Cl)Cl.[F:5][C:6]1[CH:11]=[C:10]([I:12])[CH:9]=[CH:8][C:7]=1[NH:13][C:14]1[C:15]([NH:25][S:26]([CH:29]2[CH2:32][CH:31]([O:33]CC3C=CC=CC=3)[CH2:30]2)(=[O:28])=[O:27])=[C:16]2[S:24][CH2:23][CH2:22][N:17]2[C:18](=[O:21])[C:19]=1[CH3:20].CO>C(Cl)Cl.C(Cl)(Cl)Cl>[F:5][C:6]1[CH:11]=[C:10]([I:12])[CH:9]=[CH:8][C:7]=1[NH:13][C:14]1[C:15]([NH:25][S:26]([CH:29]2[CH2:32][CH:31]([OH:33])[CH2:30]2)(=[O:27])=[O:28])=[C:16]2[S:24][CH2:23][CH2:22][N:17]2[C:18](=[O:21])[C:19]=1[CH3:20]

Participants

6

Reactant 3

HCID 887MethanolHCID 25135Boron TrichlorideHCID 583805773-Benzyloxy-cyclobutanesulfonic acid [7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridin-8-yl]-amide

Product 1

HCID 529345613-Hydroxy-cyclobutanesulfonic acid [7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridin-8-yl]-amideYield 18%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

1M BCl3 (0.46 mL, 0.468 mmol) was added to a solution of 3-benzyloxy-cyclobutanesulfonic acid [7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyridin-8-yl]-amide (0.1 g, 0.156 mmol) in dry DCM (3 mL) at −78° C. The resulting mixture was stirred at −78° C. for 3 hours. The reaction was monitored by TLC (10% MeOH in CHCl3). The reaction mixture was quenched with methanol, basified with saturated NaHCO3 solution and extracted with DCM. The organic layer was washed with brine, dried over Na2SO4 and concentrated. Purification by column chromatography on silica gel (4% MeOH in CHCl3), followed by preparative HPLC afforded 0.015 g of the product (18% yield).

Workup

  1. customThe reaction mixture was quenched with methanol
  2. extractionextracted with DCM
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by column chromatography on silica gel (4% MeOH in CHCl3)

Sources & evidence

ORD record
ord-661b96386b524288b6bf975a361f0f78
Source dataset
uspto-grants-2013_06
Patent number
US08466289B2

Reaction notes

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