Pyridine → (4aR,7aS)-6-(5-Fluoropyrimidin-2-yl)-7a-phenyl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-amine hydrochloride

HRID 1619062Notes

Reaction equation

HRID 1619062 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:16][C@@H:15]3[C@@:10]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)([N:11]=[C:12]([NH:17]C(=O)C4C=CC=CC=4)[S:13][CH2:14]3)[CH2:9]2)=[N:6][CH:7]=1.[ClH:32].CON.N1C=CC=CC=1>C(O)C>[ClH:32].[F:1][C:2]1[CH:7]=[N:6][C:5]([N:8]2[CH2:16][C@@H:15]3[C@@:10]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)([N:11]=[C:12]([NH2:17])[S:13][CH2:14]3)[CH2:9]2)=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 86762233N-[(4aR,7aS)-6-(5-Fluoropyrimidin-2-yl)-7a-phenyl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

Product 1

HCID 78318758(4aR,7aS)-6-(5-Fluoropyrimidin-2-yl)-7a-phenyl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-amine hydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of N-[(4aR,7aS)-6-(5-fluoropyrimidin-2-yl)-7a-phenyl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (215 mg, 0.496 mmol), O-methylhydroxylamine hydrochloride (207 mg, 2.48 mmol), and pyridine (392 mg, 4.96 mmol) in ethanol (5 ml) is stirred at 55° C. for 4 hours. The mixture is quenched with a solution of saturated sodium bicarbonate in water, and extracted with ethyl acetate. The organic layers are combined, dried, filtered, and concentrated under reduced pressure to give a residue. The residue is purified by silica gel flash chromatography, eluting with hexane/ethyl acetate (1:0) to hexane/ethyl acetate (0:1) to give a residue as the free base of the title compound. The residue is dissolved in 1 N hydrochloric acid (4 ml), and the solvent removed by a stream of nitrogen. The resulting solid is further purified by dissolving in 1/1 acetonitrile/methanol (4 ml) and precipitating with ethyl ether (2-3 ml). The solid is collected and dried under reduced pressure at 50° C. to give the title compound (0.10 g, 55%). ES/MS (m/e): 330 (M+H).

Workup

  1. customThe mixture is quenched with a solution of saturated sodium bicarbonate in water
  2. extractionextracted with ethyl acetate
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give a residue
  7. customThe residue is purified by silica gel flash chromatography
  8. washeluting with hexane/ethyl acetate (1:0) to hexane/ethyl acetate (0:1)

Sources & evidence

ORD record
ord-a1e8bd69953a43dfaea261070fefb14a
Source dataset
uspto-grants-2014_07
Patent number
US08772282B2

Reaction notes

Loading…