Triethylamine → HCID 70792365, compound

HRID 2405032Notes

Reaction equation

HRID 2405032 reaction equation
[C:1]([NH:8][CH2:9][C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C.[NH2:44][C:45]1[C:46]([C:50]2[N:54]([CH2:55][C:56]([C:58]3[CH:63]=[CH:62][C:61]([NH2:64])=[CH:60][CH:59]=3)=[O:57])[C:53]3[CH:65]=[CH:66][CH:67]=[CH:68][C:52]=3[N:51]=2)=[N:47][O:48][N:49]=1>CN(C=O)C.C(OCC)(=O)C.C(OCC)(=O)C.C1CCCCC1>[C:4]([O:3][C:1](=[O:2])[NH:8][CH2:9][C:10](=[O:12])[NH:64][C:61]1[CH:60]=[CH:59][C:58]([C:56](=[O:57])[CH2:55][N:54]2[C:53]3[CH:65]=[CH:66][CH:67]=[CH:68][C:52]=3[N:51]=[C:50]2[C:46]2[C:45]([NH2:44])=[N:49][O:48][N:47]=2)=[CH:63][CH:62]=1)([CH3:5])([CH3:6])[CH3:7]

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 78288N-(tert-butoxycarbonyl)glycine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 57524298HCID 57524298, compound

Product 1

HCID 70792365HCID 70792365, compoundYield 61.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolventHCID 21867204Cyclohexane ethylacetateSolvent

Procedure

To a stirred solution of 0.06 g of N-BOC-glycine (CAS 4530-20-5) (0.34 mmol; 1.2 eq.) in 1 mL of N,N′-dimethylformamide are added 0.16 g of 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.43 mmol; 1.5 eq.) and 0.1 mL of triethylamine (0.71 mmol; 2.5 eq.) at room temperature. After stirring for 0.5 h at room temperature, a solution of 0.1 g of 2-[2-(4-amino-furazan-3-yl)-benzoimidazol-1-yl]-1-(4-amino-phenyl)-ethanone (CAS 798577-83-0) (0.28 mmol; 1 eq.) in 1 mL of N,N′-dimethylformamide is added. The reaction solution is stirred overnight at room temperature. Then, a solution of 0.03 g of N-BOC-glycine (0.17 mmol; 0.6 eq.) containing 0.08 g of 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (0.22 mmol; 0.75 eq.) and 0.05 mL of triethylamine (0.35 mmol; 1.25 eq.) in 0.5 mL of N,N′-dimethylformamide is added to the reaction solution at room temperature. The same mixture is added again after additional 24 h and additional 8 h. The reaction mixture is then further stirred for 64 h (total reaction time 120 h). The reaction mixture is diluted with ethyl acetate (10 mL) and then washed with water (10 mL), 10% citric acid aqueous solution (10 mL), brine (2×5 mL), dried over magnesium sulfate, filtered and concentrated to dryness to give crude product. The crude product is subjected to silica gel column chromatography (eluent: ethyl acetate/cyclohexane=1/1 to 4/1). The obtained material is recrystallized from dichloromethane to afford 0.085 g of the desired product as a white powder.

Workup

  1. stirringThe reaction solution is stirred overnight at room temperature
  2. additionis added to the reaction solution at room temperature
  3. additionThe same mixture is added again after additional 24 h and additional 8 h
  4. stirringThe reaction mixture is then further stirred for 64 h (total reaction time 120 h)
  5. washwashed with water (10 mL), 10% citric acid aqueous solution (10 mL), brine (2×5 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customto give crude product
  10. customThe obtained material is recrystallized from dichloromethane

Sources & evidence

ORD record
ord-c277e1e69ea8483f9a56ccbf58a7c2f5
Source dataset
uspto-grants-2014_08
Patent number
US08802858B2

Reaction notes

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