Dimethylamine → HCID 24985806, compound

HRID 1188337Notes

Reaction equation

HRID 1188337 reaction equation
[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH:18]([F:20])[F:19])[N:6]2[CH:13]([CH3:17])[C:14]([OH:16])=O.[CH3:21][N:22](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:23].F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CNC>CN(C=O)C>[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH:18]([F:20])[F:19])[N:6]2[CH:13]([CH3:17])[C:14]([N:22]([CH3:23])[CH3:21])=[O:16]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57800403HCID 57800403, compound

Product 1

HCID 24985806HCID 24985806, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[4-chloro-5-cyano-2-(difluoromethyl)-1H-indol-1-yl]propanoic acid (0.010 g, 0.034 mmol) in anhydrous DMF (1.5 mL) was added HATU (0.014 g, 0.037 mmol) and DIEA (0.0048 g, 0.0037 mmol) and stirred at rt. After 10 min, dimethylamine (2M in THF, 0.17 mL, 0.34 mmol) was added and stirred at rt for 45 min. The mixture was partitioned between Et2O and 0.2N HCl. The organic phase was washed with 0.2N HCl, 0.2N NaOH and sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (0-1% MeOH—CH2Cl2 gradient) and the product was crystallized from CH2Cl2-hexanes to afford the title compound as a white solid (0.007 g, 64% yield): MS (ES) m/z 326 (M+1).

Workup

  1. stirringstirred at rt for 45 min
  2. customThe mixture was partitioned between Et2O and 0.2N HCl
  3. washThe organic phase was washed with 0.2N HCl, 0.2N NaOH
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (0-1% MeOH—CH2Cl2 gradient)
  7. customthe product was crystallized from CH2Cl2-hexanes

Sources & evidence

ORD record
ord-f1a0b33dd3c146f3a132112aabeb8550
Source dataset
uspto-grants-2014_03
Patent number
US08673948B2

Reaction notes

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