Diisopropylethylamine → 3-[5-bromo-3-[[1-[5-fluoro-2-(phenylmethoxy)phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid, methyl ester

HRID 337113Notes

Reaction equation

HRID 337113 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:6]([C:8]2([NH2:11])[CH2:10][CH2:9]2)[CH:7]=1.Br[C:21]1[C:22](=[O:39])[N:23]([C:28]2[CH:29]=[C:30]([CH:35]=[CH:36][C:37]=2[CH3:38])[C:31]([O:33][CH3:34])=[O:32])[CH:24]=[C:25]([Br:27])[N:26]=1.C(N(C(C)C)C(C)C)C>O1CCOCC1.Cl>[CH3:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7].[CH3:34][O:33][C:31](=[O:32])[C:30]1[CH:35]=[CH:36][C:37]([CH3:38])=[C:28]([N:23]2[CH:24]=[C:25]([Br:27])[N:26]=[C:21]([NH:11][C:8]3([C:6]4[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=4[O:12][CH2:13][C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH2:9][CH2:10]3)[C:22]2=[O:39])[CH:29]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 666889311-(2-(Benzyloxy)-5-fluorophenyl)cyclopropanamine

Product 2

HCID 78922-MethylpentaneHCID 666905133-[5-bromo-3-[[1-[5-fluoro-2-(phenylmethoxy)phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid, methyl esterYield 151.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 1-[5-fluoro-2-(phenylmethoxy)phenyl]-cyclopropanamine (Example 278a, 1.7 g) in dioxane (200 mL) was treated with 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 1.99 g) and N-ethyldiisopropylamine (1.7 ml), under nitrogen. The resulting solution was stirred at 100° C. for 8 h. The cooled reaction mixture was diluted with 2M HCl (300 mL), and extracted with diethyl ether (3×300 mL). The combined organics were dried (MgSO4) filtered and evaporated to afford crude product. Trituration with iso-hexane gave the subtitle compound (2.89 g).

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with diethyl ether (3×300 mL)
  3. dry with materialThe combined organics were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto afford crude product

Sources & evidence

ORD record
ord-781ce27c680c4b68b0fe25d96d340337
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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