Triethylamine → HCID 178464464, compound

HRID 2118249Notes

Reaction equation

HRID 2118249 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]([N:8]([CH3:20])[CH2:9][CH2:10][C@H:11]2[CH2:16][CH2:15][C@H:14]([C:17]([OH:19])=O)[CH2:13][CH2:12]2)=[N:6][CH:7]=1.[C:21](Cl)(=[O:25])[C:22](Cl)=O.[CH3:27][CH2:28][N:29](CC)[CH2:30][CH3:31].C[C:35]([N:37](C)C)=O>C(Cl)Cl.CN(C=O)C>[CH2:28]([N:29]([CH2:22][CH2:21][OH:25])[CH2:30][CH2:31][N:37]([CH3:35])[C:17]([C@H:14]1[CH2:13][CH2:12][C@H:11]([CH2:10][CH2:9][N:8]([C:5]2[N:6]=[CH:7][C:2]([Br:1])=[CH:3][N:4]=2)[CH3:20])[CH2:16][CH2:15]1)=[O:19])[CH3:27]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31374DimethylacetamideHCID 65578Oxalyl chlorideHCID 178483654HCID 178483654, compound

Product 1

HCID 178464464HCID 178464464, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 0.15 g (0.44 mmol) of trans-4-{2-[(5-bromo-pyrimidin-2-yl)-methyl-amino]-ethyl}-cyclohexanecarboxylic acid in 4 mL of CH2Cl2 was treated at RT with 1 drop of DMF, followed by 0.04 mL (0.48 mmol, 1.1 eq) of oxalyl chloride within 5 min, and stirring was continued for 90 min. The solution was then evaporated, the residue redissolved in acetonitrile and added dropwise to a solution of 0.29 g (1.32 mmol, 3 eq) of 2-[ethyl-(2-methylamino-ethyl)-amino]-ethanol•2HCl and 0.92 mL (6.57 mmol) of Et3N in 4 mL of DMA at 0° C. The reaction was warmed to RT and left overnight, then partitioned between Et2O(×3)/aqueous 10% NaHCO3(2×), dried over Na2SO4 and evaporated then chromatographed over silica gel (20 g) prepared in CH2Cl2:MeOH 97.5:2.5 and eluted in 95:5 to yield 0.13 g (64%) of pure trans-4-{2-[(5-bromo-pyrimidin-2-yl)-methyl-amino]-ethyl}-cyclohexanecarboxylic acid {2-[ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-methyl-amide, MS: 470 (MH+, 1Br).

Workup

  1. customThe solution was then evaporated
  2. dissolutionthe residue redissolved in acetonitrile
  3. waitleft overnight
  4. custompartitioned between Et2O(×3)/aqueous 10% NaHCO3(2×)
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customthen chromatographed over silica gel (20 g)
  8. customprepared in CH2Cl2:MeOH 97.5:2.5
  9. washeluted in 95:5

Sources & evidence

ORD record
ord-807f18a28ec9468289dfceea3cffb7b6
Source dataset
uspto-grants-2008_10
Patent number
US07442791B2

Reaction notes

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