Diisopropylethylamine → HCID 178451902, compound

HRID 1053896Notes

Reaction equation

HRID 1053896 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:10])[C:5]([NH2:9])=[CH:6][C:7]=1[F:8].[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C@H:19]1[C:23](O)=O)=[O:17])([CH3:14])([CH3:13])[CH3:12].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CS(C)=O.CCOC(C)=O>[Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]2[N:9]=[C:23]([C@@H:19]3[CH2:20][CH2:21][CH2:22][N:18]3[C:16]([O:15][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:17])[NH:10][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 199585604-Bromo-5-fluoro-1,2-benzenediamine

Product 1

HCID 178451902HCID 178451902, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-bromo-5-fluorobenzene-1,2-diamine (1.7 g, 8.4 mmol) in DMSO (42 mL) was added (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (1.8 g, 8.4 mmol) followed by HATU (3.5 g, 9.3 mmol) and N,N-diisopropyl-N-ethylamine (3.7 mL, 21.1 mmol), and the solution was stirred for 16 hours. The reaction mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4), filtered and concentrated. Acetic acid (40 mL) was added, and the mixture was stirred at 60° C. for 4 hours. Then, the reaction mixture was cooled and concentrated. The residue was azeotroped 2 times with toluene to give crude product which was purified by flash chromatography (0-50% EtOAc/hexane) to give the title compound (2.5 g, 6.4 mmol, 77%).

Workup

  1. washwashed with H2O and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionAcetic acid (40 mL) was added
  6. stirringthe mixture was stirred at 60° C. for 4 hours
  7. temperatureThen, the reaction mixture was cooled
  8. concentrationconcentrated
  9. customThe residue was azeotroped 2 times with toluene
  10. customto give crude product which
  11. customwas purified by flash chromatography (0-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-c227d3f0d2ad4476a1a05f96856c2f56
Source dataset
uspto-grants-2016_07
Patent number
US09394279B2

Reaction notes

Loading…