Ammonium Chloride → N-cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide

HRID 1697306Notes

Reaction equation

HRID 1697306 reaction equation
CO[C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]2[CH:16]=[C:15](Br)[N:14]=[C:13](Br)[C:12]2=[O:19])[CH:5]=1.C([N:24](CC)[CH:25]([CH3:27])[CH3:26])(C)C.[CH3:30][C:31]([CH3:47])([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[O:39]CC1C=CC=CC=1)[NH2:32].C1(N)CC1.C1([Mg]Br)CCCC1.[NH4+].[Cl-]>O1CCCC1.C(O)C>[CH:25]1([NH:24][C:3](=[O:20])[C:4]2[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([N:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:32][C:31]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[OH:39])([CH3:30])[CH3:47])[C:12]3=[O:19])[CH:5]=2)[CH2:27][CH2:26]1

Participants

9

Reactant 6

HCID 25517Ammonium ChlorideHCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 666888502-(2-(Benzyloxy)phenyl)propan-2-amineHCID 178419650HCID 178419650, compound

Product 1

HCID 66686301N-cyclopropyl-3-(3-(2-(2-hydroxyphenyl)propan-2-ylamino)-2-oxopyrazin-1(2H)-yl)-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °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, 0.4 g) in tetrahydrofuran (3 mL) within a microwave vial was added N,N-diisopropylethylamine (200 μL) and α,α-dimethyl-2-(phenylmethoxy)-benzenemethanamine (360 mg). The reaction was heated in a microwave for 100 minutes at 120° C. The reaction mixture was cooled to room temperature and cyclopropylamine (0.5 mL) was added. A solution of cyclopentylmagnesium bromide (2M in diethyl ether, 3 mL) was added dropwise. The reaction mixture was stirred for 30 minutes. Ethanol (2 mL) and sat. aqueous NH4Cl were added and the mixture extracted with ethyl acetate. The pooled organic were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was taken up in ethanol (3 mL) and ammonium formate (0.3 g) and 10% palladium on carbon (40 mg) were added. The reaction mixture was heated within a microwave for 30 minutes at 100° C. and then 90 minutes at 60° C. before being cooled to room temperature, then filtered and washed with ethanol. The filtrate was concentrated in vacuo. The residue was purified (SiO2 chromatography eluting with iso-hexane:ethyl acetate) to afford the subtitle compound as a solid (330 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe mixture extracted with ethyl acetate
  3. washThe pooled organic were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionammonium formate (0.3 g) and 10% palladium on carbon (40 mg) were added
  8. temperatureThe reaction mixture was heated within a microwave for 30 minutes at 100° C.
  9. temperature90 minutes at 60° C. before being cooled to room temperature
  10. filtrationfiltered
  11. washwashed with ethanol
  12. concentrationThe filtrate was concentrated in vacuo
  13. customThe residue was purified
  14. wash(SiO2 chromatography eluting with iso-hexane:ethyl acetate)

Sources & evidence

ORD record
ord-d021d43f20fc4b168a798ffcbb244558
Source dataset
uspto-grants-2012_04
Patent number
US08163905B2

Reaction notes

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