2-Chloropyrimidine → HCID 86762236, compound

HRID 1619048Notes

Reaction equation

HRID 1619048 reaction equation
[F:1][C:2]1[S:6][C:5]([C:7]23[CH2:15][NH:14][CH2:13][CH:12]2[CH2:11][S:10][C:9]([NH:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:8]3)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Cl[C:35]1[N:40]=[CH:39][CH:38]=[CH:37][N:36]=1>O1CCOCC1.C(OCC)(=O)C>[F:1][C:2]1[S:6][C:5]([C:7]23[CH2:15][N:14]([C:35]4[N:40]=[CH:39][CH:38]=[CH:37][N:36]=4)[CH2:13][CH:12]2[CH2:11][S:10][C:9]([NH:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:8]3)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 744042-ChloropyrimidineHCID 81531DiisopropylethylamineHCID 86762237HCID 86762237, compound

Product 1

HCID 86762236HCID 86762236, compoundYield 69.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred mixture of N-[7a-(5-fluoro-2-thienyl)-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (127 mg, 0.351 mmol) in 1,4-dioxane (7.0 mL) is added diisopropylethylamine (0.184 mL, 1.05 mmol) and 2-chloropyrimidine (402 mg, 3.51 mmol). The solution is heated to reflux for 2 hours then is cooled, diluted with ethyl acetate, (60 mL) and washed with dilute sodium bicarbonate (30 mL, prepared from saturated sodium bicarbonate (15 mL) and water (15 mL), water (30 mL) and brine (30 mL). The organic phase is dried over sodium sulfate, filtered, and concentrated. The residue is purified by silica gel chromatography eluting with dichloromethane/methanol (gradient from 99:1 to 96:4) to give after concentration a residue which is further purified by silica gel chromatography eluting with hexanes/ethyl acetate (gradient from 60:40 to 30:70) to give the title compound (107 mg, 69%). ES/MS (m/e): 440 (M+H).

Workup

  1. temperatureThe solution is heated
  2. temperatureto reflux for 2 hours
  3. temperaturethen is cooled
  4. washwashed with dilute sodium bicarbonate (30 mL
  5. customprepared from saturated sodium bicarbonate (15 mL) and water (15 mL), water (30 mL) and brine (30 mL)
  6. dry with materialThe organic phase is dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is purified by silica gel chromatography
  10. washeluting with dichloromethane/methanol (gradient from 99:1 to 96:4)
  11. customto give
  12. concentrationafter concentration a residue which
  13. customis further purified by silica gel chromatography
  14. washeluting with hexanes/ethyl acetate (gradient from 60:40 to 30:70)

Sources & evidence

ORD record
ord-c62f16677b6d47cfa3afe9310e082b60
Source dataset
uspto-grants-2014_07
Patent number
US08772282B2

Reaction notes

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