Diisopropylethylamine → HCID 178522684, compound

HRID 1967017Notes

Reaction equation

HRID 1967017 reaction equation
COC(=O)[CH2:4][NH:5][C:6](=[O:37])[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:21]([N:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:26]([CH:33]3[CH2:35][CH2:34]3)[CH2:25][CH2:24]2)=[O:22])=[CH:9][C:8]=1[Cl:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.NC1[NH:77][N:76]=[N:75][N:74]=1>CN(C)C=O>[Cl:36][C:8]1[CH:9]=[C:10]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:21]([N:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:26]([CH:33]3[CH2:35][CH2:34]3)[CH2:25][CH2:24]2)=[O:22])[C:11]([Cl:13])=[CH:12][C:7]=1[C:6]([NH:5][C:4]1[NH:77][N:76]=[N:75][N:74]=1)=[O:37]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 53312194{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoylamino}-acetic acid methyl esterHCID 178509299HCID 178509299, compound

Product 1

HCID 178522684HCID 178522684, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.20 g (0.41 mmol) 2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoic acid (Example 29, intermediate) in 2 mL N,N-dimethylformamide were added 0.165 g (0.43 mmol) 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, commercially available, CAS RN 148893-10-1) and 0.21 mL (1.24 mmol) N,N-diisopropylethylamine. To the yellow solution 0.037 g (0.43 mmol) 5-amino-1H-tetrazole (commercially available, CAS RN 4418-61-5) was added and the solution was stirred at room temperature for 3.25 hours. Then the solution was heated to 60° C. and stirred at this temperature for 88 hours. After filtration over a syringe micro filter, the reaction mixture was purified by preparative HPLC (Phenomenex Gemini column) with a gradient of acetonitrile:water (containing 0.05% formic acid) (10:90 to 98:2) to give the desired compound as a light brown solid (0.051 g, 22%). MS (ESI): m/z=551.11 [M+H]+.

Workup

  1. temperatureThen the solution was heated to 60° C.
  2. stirringstirred at this temperature for 88 hours
  3. filtrationAfter filtration over a syringe micro filter
  4. customthe reaction mixture was purified by preparative HPLC (Phenomenex Gemini column) with a gradient of acetonitrile

Sources & evidence

ORD record
ord-e26641ad69f74505b6bdfa2260ee8fc7
Source dataset
uspto-grants-2013_04
Patent number
US08420647B2

Reaction notes

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