Pyridine → HCID 69359664, compound

To a solution of methyl 4-amino-1H-indole-6-carboxylate (D201) (1.0 g, 5.3 mmol, 1 equiv) in CH2Cl2 (50 ml) were added pyridine (0.55 g, 6.5 mmol, 1.2 equiv), 4-chloro-1-butanesulfonyl chloride (1.14 g, 6 mmol, 1.1 equiv) and DMAP (300 mg, 2.45 mmol, 0.5 equiv) and the resulting mixture was stirred at room temperature for 5 h. NEt3 (1 ml, 7.2 mmol, 1.3 equiv) was added and the resulting solution stirred for 2 h then diluted with AcOEt, washed with a 2N aqueous solution, a saturated aqueous NaHCO3 solution, dried over MgSO4 and concentrated in vacuo. The residue was dissolved in MeOH (20 ml) and treated with a 2N aqueous NaOH solution (10 ml, 20 mmol, excess). The resulting solution was stirred at room temperature for 15 h then most of the MeOH was removed in vacuo. The residue was partitioned between AcOEt and a 2N aqueous HCl solution. The two layers were separated and the organic phase was dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (CH2Cl2/MeOH: 9/1) gave 4-(1,1-dioxidotetrahydro-2H-1,2-thiazin-2-yl)-1H-indole-6-carboxylic acid (A155) (320 mg, 20%) as a pale pink solid. [M+H]=295.0, RT=1.90 min.

1. stirringthe resulting solution stirred for 2 h
2. washwashed with a 2N aqueous solution
3. dry with materiala saturated aqueous NaHCO3 solution, dried over MgSO4
4. concentrationconcentrated in vacuo
5. dissolutionThe residue was dissolved in MeOH (20 ml)
6. stirringThe resulting solution was stirred at room temperature for 15 h
7. custommost of the MeOH was removed in vacuo
8. customThe residue was partitioned between AcOEt
9. customThe two layers were separated
10. dry with materialthe organic phase was dried over MgSO4
11. concentrationconcentrated in vacuo
12. customPurification of the residue by flash chromatography on silica gel (CH2Cl2/MeOH: 9/1)

ORD record

ord-78da821f9ff440699a3349d686471a2d

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07253198B2