Diisopropylethylamine → {2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoylamino}-acetic acid methyl ester

HRID 1025854Notes

Reaction equation

HRID 1025854 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=2[C:18]([N:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]([CH:30]3[CH2:32][CH2:31]3)[CH2:22][CH2:21]2)=[O:19])[C:8]([Cl:33])=[CH:7][C:3]=1[C:4](O)=[O:5].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.[CH3:68][O:69][C:70](=[O:73])[CH2:71][NH2:72]>CN(C)C=O>[CH3:68][O:69][C:70](=[O:73])[CH2:71][NH:72][C:4](=[O:5])[C:3]1[CH:7]=[C:8]([Cl:33])[C:9]([O:11][C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=2[C:18]([N:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]([CH:30]3[CH2:31][CH2:32]3)[CH2:22][CH2:21]2)=[O:19])=[CH:10][C:2]=1[Cl:1]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 673205762,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoic acid

Product 1

HCID 53312194{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoylamino}-acetic acid methyl esterYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.18 g (0.37 mmol) 2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoic acid in 2 mL N,N-dimethylformamide were added 0.148 g (0.39 mmol) O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, commercially available, CAS RN 148893-10-1) and 0.25 mL (1.49 mmol) N,N-diisopropylethylamine. To the light brown solution 0.049 g (0.39 mmol) glycine methyl ester hydrochloride (commercially available, CAS RN 5680-79-5) was added and the solution was stirred at room temperature for 2.5 hours. The solution was poured on water and extracted three times with ethyl acetate. The combined organic layers were washed twice with water and brine, dried over magnesium sulfate, filtered, treated with silica gel and evaporated. The resulting powder was purified by silica gel chromatography using a MPLC system (10 g silica gel column, CombiFlash Companion, Isco Inc.) with a gradient of n-heptane:ethyl acetate (100:0 to 0:100) to yield 0.169 g (82%) of the desired compound as a light brown solid. MS (ESI): m/z=555.12 [M+H]+.

Workup

  1. additionThe solution was poured on water
  2. extractionextracted three times with ethyl acetate
  3. washThe combined organic layers were washed twice with water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. additiontreated with silica gel
  7. customevaporated
  8. customThe resulting powder was purified by silica gel chromatography

Sources & evidence

ORD record
ord-15a324d6de1c432b8cebd144307bfad3
Source dataset
uspto-grants-2014_05
Patent number
US08729091B2

Reaction notes

Loading…