Triethylamine → N-[(4aR,7aS)-6-(5-Fluoropyrimidin-2-yl)-7a-phenyl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 1619043Notes

Reaction equation

HRID 1619043 reaction equation
[C:1]1([C@:7]23[CH2:15][NH:14][CH2:13][C@H: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:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:25][C:26]1[CH:27]=[N:28][C:29](Cl)=[N:30][CH:31]=1.O1CCOCC1.C(N(CC)CC)C>O>[F:25][C:26]1[CH:27]=[N:28][C:29]([N:14]2[CH2:13][C@@H:12]3[C@@:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)([N:8]=[C:9]([NH:16][C:17](=[O:24])[C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[S:10][CH2:11]3)[CH2:15]2)=[N:30][CH:31]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 312751,4-DioxaneHCID 5834662-Chloro-5-fluoropyrimidineHCID 86762229N-[(4aR,7aS)-7a-Phenyl-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

Product 1

HCID 86762233N-[(4aR,7aS)-6-(5-Fluoropyrimidin-2-yl)-7a-phenyl-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamideYield 80%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of N-[(4aR,7aS)-7a-phenyl-4a,5,6,7-tetrahydro-4H-pyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (250 mg, 0.629 mmol), 5-fluoro-2-chloropyrimidine (167 mg, 1.26 mmol), 1,4-dioxane (10 mL), and triethylamine (318 mg, 3.14 mmol) is stirred at 110° C. for 4 hours. The reaction is cooled, diluted with water and extracted with dichloromethane. 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 the title compound (0.217 g, 80%). ES/MS (m/e): 434 (M+H).

Workup

  1. temperatureThe reaction is cooled
  2. extractionextracted with dichloromethane
  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-bfc19e53a71e4fbbbf2f4e4cca7b4948
Source dataset
uspto-grants-2014_07
Patent number
US08772282B2

Reaction notes

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