Triethylamine → HCID 178520558, compound

HRID 1480459Notes

Reaction equation

HRID 1480459 reaction equation
[NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[CH:12]=2)=[O:8])[CH2:3]1.[NH:19]1[CH:23]=[C:22]([CH2:24][CH2:25][CH2:26][C:27](O)=[O:28])[N:21]=[N:20]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C)C=O>[NH:19]1[CH:23]=[C:22]([CH2:24][CH2:25][CH2:26][C:27]([NH:1][CH:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]3[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[CH:12]=3)=[O:8])[CH2:3]2)=[O:28])[N:21]=[N:20]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86722684HCID 86722684, compoundHCID 178525383HCID 178525383, compound2×

Product 1

HCID 178520558HCID 178520558, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture comprising of 3,5-dichlorobenzyl 3-aminopyrrolidine-1-carboxylate (1 equiv), 4-(1H-1,2,3-triazol-4-yl)butanoic acid (1 equiv.), HATU (1.5 equiv.) and triethylamine (5 equiv.) in dimethylformamide was stirred at RT for 18 hours. Another 1 equivalent of 4-(1H-1,2,3-triazol-4-yl)butanoic acid was added to the reaction mixture and stirring continued for a further 2 hours. The reaction mixture was concentrated under reduced pressure, diluted with water and extracted with DCM. The organic portion was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was dry loaded using silica onto a 12 g ISCO column, eluting with 0-15% MeOH in DCM. The product fractions were combined and concentrated under reduced pressure. Further purification was carried our using preparative LC-MS. The product fractions were concentrated under reduced pressure to give an aqueous solution and extracted with EtOAc to afford the title compound;

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with water
  3. extractionextracted with DCM
  4. customThe organic portion was separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dry with materialThe crude product was dry
  9. washeluting with 0-15% MeOH in DCM
  10. concentrationconcentrated under reduced pressure
  11. customFurther purification
  12. concentrationThe product fractions were concentrated under reduced pressure
  13. customto give an aqueous solution
  14. extractionextracted with EtOAc

Sources & evidence

ORD record
ord-b118fac3c7e34e2282ffb9d7096436da
Source dataset
uspto-grants-2016_08
Patent number
US09409895B2

Reaction notes

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