Pyridine → HCID 89832359, compound

HRID 470284Notes

Reaction equation

HRID 470284 reaction equation
[F:1][C:2]1[S:6][C:5]([C:7]23[CH2:15][N:14]([C:16]4[N:21]=[CH:20][CH:19]=[CH:18][N:17]=4)[CH2:13][CH:12]2[CH2:11][S:10][C:9]([NH:22]C(=O)C2C=CC=CC=2)=[N:8]3)=[CH:4][CH:3]=1.N1C=CC=CC=1.Cl.CON>C(O)C.C(OCC)(=O)C>[F:1][C:2]1[S:6][C:5]([C:7]23[CH2:15][N:14]([C:16]4[N:17]=[CH:18][CH:19]=[CH:20][N:21]=4)[CH2:13][CH:12]2[CH2:11][S:10][C:9]([NH2:22])=[N:8]3)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 86762236HCID 86762236, compound

Product 1

HCID 89832359HCID 89832359, compoundYield 85.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
58 °C

Procedure

To a stirred solution of the N-[7a-(5-fluoro-2-thienyl)-6-pyrimidin-2-yl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (100 mg, 0.228 mmol) in ethanol (4.6 mL) is added pyridine (0.184 mL, 2.28 mmol) and O-methylhydroxylamine hydrochloride (190 mg, 2.28 mmol). The resulting mixture is heated at 58° C. for 15 hours. The solution is allowed to cool to room temperature, diluted with ethyl acetate (25 mL), and washed with dilute sodium bicarbonate ((20 mL) prepared from water (10 mL) and saturated sodium bicarbonate (10 mL)). The aqueous phase is extracted with ethyl acetate (25 mL). The combined organic extracts are dried over sodium sulfate, filtered, and concentrated. The residue is purified by silica gel flash chromatography eluting with dichloromethane/7 M ammonia in methanol, gradient from 99:1 to 95:5, to give the title compound (65 mg, 0.194 mmol, 85%) as a white solid. ES/MS (m/e): 336 (M+H).

Workup

  1. temperatureto cool to room temperature
  2. washwashed with dilute sodium bicarbonate ((20 mL) prepared from water (10 mL) and saturated sodium bicarbonate (10 mL))
  3. extractionThe aqueous phase is extracted with ethyl acetate (25 mL)
  4. dry with materialThe combined organic extracts are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel flash chromatography
  8. washeluting with dichloromethane/7 M ammonia in methanol, gradient from 99:1 to 95:5

Sources & evidence

ORD record
ord-04297f7866db43cbafd79904505b4dc4
Source dataset
uspto-grants-2014_01
Patent number
US08629270B2

Reaction notes

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