Triethylamine → HCID 86642114, compound

HRID 1943241Notes

Reaction equation

HRID 1943241 reaction equation
Cl.O[CH2:3][C@H:4]1[N:14]2[C:15]3[N:6]([C:7](=[O:17])[CH2:8][CH2:9][C:10]=3[CH:11]=[CH:12][C:13]2=[O:16])[CH2:5]1.C(N(CC)CC)C.CS(Cl)(=O)=O.CS([O-])(=O)=O.[F:35][C:36]([F:47])([F:46])[C:37]([NH:39][CH2:40][C@@H:41]1[CH2:45][CH2:44][NH:43][CH2:42]1)=[O:38]>C(Cl)Cl>[O:16]=[C:13]1[CH:12]=[CH:11][C:10]2[CH2:9][CH2:8][C:7](=[O:17])[N:6]3[CH2:5][C@@H:4]([CH2:3][N:43]4[CH2:44][CH2:45][C@@H:41]([CH2:40][NH:39][C:37](=[O:38])[C:36]([F:46])([F:47])[F:35])[CH2:42]4)[N:14]1[C:15]=23

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 59254366HCID 59254366, compoundHCID 68596275HCID 68596275, compound

Product 1

HCID 86642114HCID 86642114, compoundYield 37.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a 100 mL round-bottomed flask was added (1S)-1-(hydroxymethyl)-1,2,5,6-tetrahydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione HCl (for a preparation see Example 47(c)) (350 mg, 1.589 mmol), triethylamine (0.266 ml, 1.907 mmol) in DCM (20 ml) 0° C. to give a orange solution. Methane sulfonylchloride (0.135 ml, 1.748 mmol) was added and the reaction was allowed to warm to rt and stir for 1 h. LCMS indicated that the methanesulfonate had formed. The reaction was diluted with DCM (100 mL) and washed with 2×25 mL of a saturated aqueous NaHCO3 solution. The organic phase was separated and dried over Na2SO4. The solution was concentrated under vacuum, diluted with acetonitrile (20.00 ml) and pyridine (0.500 ml) was added. 2,2,2-trifluoro-N-[(3R)-3-pyrrolidinylmethyl]acetamide (550 mg, 2.364 mmol) was added and the reaction was heated to 80° C. and stirred for 25 h. LCMS indicated a complete reaction. The reaction was cooled to rt and concentrated under vacuum. The reaction mixture was diluted with DCM (100 mL) and washed with 25 mL of a saturated NaHCO3 solution. The organic phase was separated and dried over Na2SO4. The crude product was purified on silica eluting with 0-15% MeOH/DCM to give product (240 mg, 0.602 mmol, 37.9% yield) as a pale yellow oil.

Workup

  1. customto give a orange solution
  2. customhad formed
  3. washwashed with 2×25 mL of a saturated aqueous NaHCO3 solution
  4. customThe organic phase was separated
  5. dry with materialdried over Na2SO4
  6. concentrationThe solution was concentrated under vacuum
  7. additiondiluted with acetonitrile (20.00 ml) and pyridine (0.500 ml)
  8. additionwas added
  9. temperaturethe reaction was heated to 80° C.
  10. stirringstirred for 25 h
  11. customa complete reaction
  12. temperatureThe reaction was cooled to rt
  13. concentrationconcentrated under vacuum
  14. additionThe reaction mixture was diluted with DCM (100 mL)
  15. washwashed with 25 mL of a saturated NaHCO3 solution
  16. customThe organic phase was separated
  17. dry with materialdried over Na2SO4
  18. customThe crude product was purified on silica eluting with 0-15% MeOH/DCM

Sources & evidence

ORD record
ord-82007a04e6b5407497bba323e63340bc
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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