Tyramine → HCID 66685793, compound

HRID 337045Notes

Reaction equation

HRID 337045 reaction equation
Br[C:2]1[C:3](=[O:20])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:12]([O:14]C)=O)[CH:5]=[C:6](Br)[N:7]=1.[NH2:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1.Cl.ClCC[N:35]1[CH2:39][CH2:38][CH2:37]C1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:46]([N:48]([CH2:51][CH3:52])[CH2:49][CH3:50])[CH3:47]>O1CCCC1.CN(C)C=O>[CH:39]1([NH:35][C:12](=[O:14])[C:11]2[CH:16]=[CH:17][C:18]([CH3:19])=[C:9]([N:4]3[CH:5]=[CH:6][N:7]=[C:2]([NH:21][CH2:22][CH2:23][C:24]4[CH:29]=[CH:28][C:27]([O:30][CH2:47][CH2:46][N:48]5[CH2:51][CH2:52][CH2:50][CH2:49]5)=[CH:26][CH:25]=4)[C:3]3=[O:20])[CH:10]=2)[CH2:37][CH2:38]1

Participants

8

Reactant 5

HCID 5610TyramineHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoate

Product 1

HCID 66685793HCID 66685793, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

To a stirred solution of 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 0.1 g) in tetrahydrofuran (2 mL) was added triethylamine (0.17 mL) and 4-(2-aminoethyl)-phenol (34 mg). The reaction mixture was stirred for 12 h and 1-(2-chloroethyl)-pyrrolidine hydrochloride (120 mg), cesium carbonate (646 mg) and N,N-dimethylformamide (2 mL) were added. The mixture was heated within a microwave at 130° C. for 100 minutes. The reaction mixture was cooled to room temperature and quenched with sat. NaHCO3. The mixture was extracted with dichloromethane. The pooled organics were washed with water and brine, dried (Na2SO4), filtered and the solvent removed. The product was taken up in tetrahydrofuran (3 mL) followed by the addition of cyclopropylamine (0.15 mL) and cyclopentylmagnesium bromide (2M in diethyl ether, 0.75 mL) portionwise. The reaction mixture was stirred under nitrogen for 1 h before the addition of ethanol (2 mL), ammonium formate (300 mg) and 10% palladium on carbon (30 mg). The reaction mixture was heated within a microwave at 100° C. for 60 minutes, filtered and washed with ethanol. The filtrate was concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound (60 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with sat. NaHCO3
  3. extractionThe mixture was extracted with dichloromethane
  4. washThe pooled organics were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent removed
  8. additionfollowed by the addition of cyclopropylamine (0.15 mL) and cyclopentylmagnesium bromide (2M in diethyl ether, 0.75 mL) portionwise
  9. stirringThe reaction mixture was stirred under nitrogen for 1 h before the addition of ethanol (2 mL), ammonium formate (300 mg) and 10% palladium on carbon (30 mg)
  10. temperatureThe reaction mixture was heated within a microwave at 100° C. for 60 minutes
  11. filtrationfiltered
  12. washwashed with ethanol
  13. concentrationThe filtrate was concentrated in vacuo
  14. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Sources & evidence

ORD record
ord-93eedc6d1de34ef099f31e1e1325866f
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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