Trifluoroacetic acid → N-[4-(3,4,5,6-Tetrahydro-2H-[1,2']bipyrazinyl-3'-yl)-benzyl]-acetamide

HRID 220570Notes

Reaction equation

HRID 220570 reaction equation
C(O)(C(F)(F)F)=O.C(OC([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[C:26]([C:27]3[CH:32]=[CH:31][C:30]([CH2:33][NH:34][C:35](=[O:37])[CH3:36])=[CH:29][CH:28]=3)=[N:25][CH:24]=[CH:23][N:22]=2)[CH2:17][CH2:16]1)=O)(C)(C)C>C(Cl)Cl>[N:18]1([C:21]2[C:26]([C:27]3[CH:28]=[CH:29][C:30]([CH2:33][NH:34][C:35](=[O:37])[CH3:36])=[CH:31][CH:32]=3)=[N:25][CH:24]=[CH:23][N:22]=2)[CH2:19][CH2:20][NH:15][CH2:16][CH2:17]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 685946133'-[4-(Acetylamino-methyl)-phenyl]-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid tert-butyl ester

Product 1

HCID 68595017N-[4-(3,4,5,6-Tetrahydro-2H-[1,2']bipyrazinyl-3'-yl)-benzyl]-acetamideYield 92.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add TFA (0.6 mL, 7.94 mmol) to a solution of 3′-[4-(Acetylamino-methyl)-phenyl]-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (650 mg, 1.58 mmol) in DCM (6.5 mL) and maintain stirring for 3 hr. Concentrate material to dryness. Redissolve in DCM (10 mL) and add TFA (1.2 mL). Heat reaction mixture at 40° C. for 3 hr. Purify the mixture by SCX-2® ion exchange chromatography, eluting with 2 M NH3 in MeOH to give the title compound as a yellow oil (454 mg, 92%). 1H-NMR (400 MHz, CDCl3) δ 8.14 (d, 1H), 8.08 (d, 1H), 7.90 (d, 2H), 7.36 (d, 2H), 5.81 (bs, 1H), 4.49 (d, 2H), 3.17 (m, 4H), 2.88 (m, 4H), 2.06 (s, 3H).

Workup

  1. temperaturemaintain
  2. temperatureHeat
  3. customreaction mixture at 40° C. for 3 hr
  4. customPurify the mixture by SCX-2® ion exchange chromatography
  5. washeluting with 2 M NH3 in MeOH

Sources & evidence

ORD record
ord-3af1db74085348998b45286d61af24fd
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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