Trifluoroacetic acid → benzyl 2-[3-chloro-2-methyl-5-(3-[(methylamino)methyl]phenethylamino)-6-oxo-1(6H)-pyrazinyl]acetate

HRID 2228732Notes

Reaction equation

HRID 2228732 reaction equation
[CH2:1]([O:8][C:9](=[O:39])[CH2:10][N:11]1[C:16]([CH3:17])=[C:15]([Cl:18])[N:14]=[C:13]([NH:19][CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][N:29](C(OC(C)(C)C)=O)[CH3:30])[CH:23]=2)[C:12]1=[O:38])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:18][C:15]1[N:14]=[C:13]([NH:19][CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][NH:29][CH3:30])[CH:23]=2)[C:12](=[O:38])[N:11]([CH2:10][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:39])[C:16]=1[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 18470853Benzyl 2-[3-[(3-[(tert-Butoxycarbonyl)(methyl)amino]methylphenethyl)amino]-5-chloro-6-methyl-2-oxo-1(2H)-pyrazinyl]acetate

Product 1

HCID 18470865benzyl 2-[3-chloro-2-methyl-5-(3-[(methylamino)methyl]phenethylamino)-6-oxo-1(6H)-pyrazinyl]acetateYield 66.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Benzyl-2-[3-[(3-[(tert-butoxycarbonyl)(methyl)amino]methylphenethyl)amino]-5-chloro-6-methyl-2-oxo-1(2H)-pyrazinyl]acetate (preparation 18) (0.7 g, 1.26 mmol) was dissolved in CH2Cl2 (10 ml) and treated with TFA (1.0 ml). After stirring at room temperature for 3 hr, the reaction mixture was evaporated to dryness then dissolved in ethyl acetate (200 ml) washed with sat. aq NaHCO3, sat aq brine, dried over MgSO4. Removal of the drying agent by filtration followed by evaporation of the solvent gave a dark brown oil which was purified by chromatography (SiO2, gradient elution with 100% CH2Cl2; 98:2 CH2Cl2:MeOH; 95:5 CH2Cl2:MeOH; 95:5:1 CH2Cl2:MeOH:NH3) to give the desired product (0.38 g, 65%). 1H NMR (CDCl3) δ 2.00 (s, br, 1H), 2.20 (s, 3H), 2.45 (s, 3H), 2.90 (t, 2H), 3.70 (m, 2H), 3.75 (s, 2H), 4.80 (s, 2H), 5.20 (s, 2H), 6.10 (m, br, 1H), 7.10 (m, 1H), 7.15 (m, 2H), 7.25 (m, 1H), 7.35 (m, 5H). LRMS m/z=455.0, 457.2 (M+1)+.

Workup

  1. customthe reaction mixture was evaporated to dryness
  2. dissolutionthen dissolved in ethyl acetate (200 ml)
  3. washwashed with sat. aq NaHCO3
  4. dry with materialdried over MgSO4
  5. customRemoval of the drying agent
  6. filtrationby filtration
  7. customfollowed by evaporation of the solvent
  8. customgave a dark brown oil which
  9. customwas purified by chromatography (SiO2, gradient elution with 100% CH2Cl2; 98:2 CH2Cl2:MeOH; 95:5 CH2Cl2:MeOH; 95:5:1 CH2Cl2:MeOH:NH3)

Sources & evidence

ORD record
ord-6483985a18fc4d78b5097059f5e4a7af
Source dataset
uspto-grants-2002_07
Patent number
US06417203B1

Reaction notes

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