Diisopropylethylamine → [2-Chloro-4-(2,5-dichloro-phenoxy)-6-methyl-pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone

HRID 1025899Notes

Reaction equation

HRID 1025899 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]([CH3:11])[CH:8]=[C:7]([O:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[Cl:20])[C:3]=1[C:4]([O-:6])=O.[Li+].C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:55]1([N:58]2[C:67]3[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=3)[NH:61][CH2:60][CH2:59]2)[CH2:57][CH2:56]1>CN(C)C=O>[Cl:1][C:2]1[C:3]([C:4]([N:61]2[C:62]3[C:67](=[CH:66][CH:65]=[CH:64][CH:63]=3)[N:58]([CH:55]3[CH2:57][CH2:56]3)[CH2:59][CH2:60]2)=[O:6])=[C:7]([O:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[Cl:20])[CH:8]=[C:9]([CH3:11])[N:10]=1

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)HCID 673207551-Cyclopropyl-1,2,3,4-tetrahydroquinoxalineHCID 86655954Lithium 2-chloro-4-(2,5-dichloro-phenoxy)-6-methyl-nicotinate

Product 1

HCID 53311615[2-Chloro-4-(2,5-dichloro-phenoxy)-6-methyl-pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanoneYield 25.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 120 mg (0.355 mmol) lithium 2-chloro-4-(2,5-dichloro-phenoxy)-6-methyl-nicotinate in 3 mL dry N,N-dimethylformamide was added 0.30 mL (1.773 mmol) N-ethyldiisopropylamine and 163 mg (0.425 mmol) O-(7-azabenzotriazol-1-yl)-N,N,N;N′-tetramethyluronium hexafluorophosphate (HATU, commercially available, CAS RN 148893-10-1) and 74 mg (0.425 mmol) 1-cyclopropyl-1,2,3,4-tetrahydro-quinoxaline (Example 8, intermediate a). The reaction mixture was stirred for 18 hours at room temperature and evaporated. The residue was purified on a preparative HPLC system (Phenomenex Gemini column) using a gradient of acetonitrile:water (containing 0.05% formic acid) (50:50 to 100:0) to provide 45 mg (26%) of the title compound as a light yellow foam (30%). MS (ESI): m/z=488.07 [M+H]+.

Workup

  1. customevaporated
  2. customThe residue was purified on a preparative HPLC system (Phenomenex Gemini column)

Sources & evidence

ORD record
ord-5f17e5a011244c709b06ce7d6b0e7767
Source dataset
uspto-grants-2014_05
Patent number
US08729091B2

Reaction notes

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