Propane, 1-chloro-3-isocyanato- → HCID 59625599, compound

HRID 2192827Notes

Reaction equation

HRID 2192827 reaction equation
[NH2:1][C@@H:2]1[CH2:7][C@H:6]([N:8]([C:13]([C:15]2[C:16]([NH:25][CH2:26][CH2:27][CH2:28][S:29][CH3:30])=[N:17][C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])=[N:19][CH:20]=2)=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11])[CH2:5][N:4]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:3]1.CC(C)([O-])C.[K+].Cl[CH2:45][CH2:46][CH2:47][N:48]=[C:49]=[O:50]>ClCCCl.C1COCC1.O>[C:21]([C:18]1[N:17]=[C:16]([NH:25][CH2:26][CH2:27][CH2:28][S:29][CH3:30])[C:15]([C:13]([N:8]([CH2:9][CH:10]([CH3:12])[CH3:11])[C@H:6]2[CH2:7][C@@H:2]([N:1]3[CH2:45][CH2:46][CH2:47][NH:48][C:49]3=[O:50])[CH2:3][N:4]([C:31]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:32])[CH2:5]2)=[O:14])=[CH:20][N:19]=1)([CH3:24])([CH3:22])[CH3:23]

Participants

7

Reactant 3

HCID 166752Propane, 1-chloro-3-isocyanato-HCID 23665647Potassium tert-butoxideHCID 59625415HCID 59625415, compound

Product 1

HCID 59625599HCID 59625599, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl (3R,5S)-3-amino-5-{[(2-tert-butyl-4-{[3-(methylsulfanyl)propyl]amino}pyrimidin-5-yl)carbonyl](2-methylpropyl)amino}piperidine-1-carboxylate (97 mg) was dissolved in 1,2-dichloroethane (2 ml)-THF (2 ml), chloropropyl isocyanate (25 μl) was added, and the mixture was stirred at room temperature for 1 hr. Potassium tert-butoxide (30 mg) was added and the reaction mixture was stirred at room temperature for 8 hr, and further at 60° C. for 12 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in THF (4 ml), sodium hydride (50% contained, 26 mg) was added under ice-cooling, and the mixture was stirred under ice-cooling for 4 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, eluted with ethyl acetate-methanol (100:0-90:10) and concentrated under reduced pressure to give the object compound (103 mg).

Workup

  1. additionwas added
  2. stirringthe reaction mixture was stirred at room temperature for 8 hr
  3. waitfurther at 60° C. for 12 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. dissolutionThe residue was dissolved in THF (4 ml)
  9. additionsodium hydride (50% contained, 26 mg) was added under ice-
  10. temperaturecooling
  11. stirringthe mixture was stirred under ice-
  12. temperaturecooling for 4 hr
  13. additionThe reaction mixture was diluted with water
  14. extractionthe mixture was extracted with ethyl acetate
  15. washThe extract was washed with saturated brine
  16. dry with materialdried over anhydrous magnesium sulfate
  17. customThe solvent was evaporated under reduced pressure
  18. washeluted with ethyl acetate-methanol (100:0-90:10)
  19. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f3efcc96332947baa233988c7b7a1e6b
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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