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

HRID 1877419Notes

Reaction equation

HRID 1877419 reaction equation
[Br:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([O:6][C:7]2[N:15]=[CH:14][CH:13]=[CH:12][C:8]=2[C:9]([OH:11])=O)=[C:4]([Cl:19])[CH:3]=1.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:53]1([N:56]2[C:65]3[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=3)[NH:59][CH2:58][CH2:57]2)[CH2:55][CH2:54]1.C([O-])(O)=O.[Na+]>ClCCl>[Br:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([O:6][C:7]2[C:8]([C:9]([N:59]3[C:60]4[C:65](=[CH:64][CH:63]=[CH:62][CH:61]=4)[N:56]([CH:53]4[CH2:55][CH2:54]4)[CH2:57][CH2:58]3)=[O:11])=[CH:12][CH:13]=[CH:14][N:15]=2)=[C:4]([Cl:19])[CH:3]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 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 673686592-(4-Bromo-2,5-dichloro-phenoxy)-nicotinic acid

Product 1

HCID 59294468[2-(4-Bromo-2,5-dichloro-phenoxy)-pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-bromo-2,5-dichloro-phenoxy)-nicotinic acid (50 mg, 0.14 mmol, 1.0 equiv) in anhydrous dichloromethane (1.5 mL) was added N-ethyldiisopropylamine (36 mg, 47 μL, 0.28 mmol, 2.0 equiv; [CAS RN 7087-68-5]) and HATU (68 mg, 0.18 mmol, 1.3 equiv; [CAS RN 148893-10-1]) and the reaction mixture stirred at rt. After 10 min, 1-cyclopropyl-1,2,3,4-tetrahydro-quinoxaline (29 mg, 0.17 mmol, 1.2 equiv; Example 125, Step 5) was added and stirring at rt continued over night. To the reaction was added a sat. solution of NaHCO3 (20 mL) and the solution extracted with dichloromethane (3×20 mL). The combined organic phases were dried over Na2SO4 and the product purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate affording 45 mg (63%) of the title compound as an off-white powder. MS (ISP): 520.3 [M+H]+.

Workup

  1. stirringstirring at rt
  2. waitcontinued over night
  3. extractionthe solution extracted with dichloromethane (3×20 mL)
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. customthe product purified by silica column chromatography
  6. washeluting with a gradient of heptane/ethyl acetate affording 45 mg (63%) of the title compound as an off-white powder

Sources & evidence

ORD record
ord-5e230a47ff3a40c8a8cda972aea0234b
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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