Trifluoroacetic acid → HCID 44512786, compound

HRID 1183018Notes

Reaction equation

HRID 1183018 reaction equation
[CH3:1][O:2][C:3]1[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[CH:39][C:4]=1[CH2:5][NH:6][CH:7]([CH2:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:31][C@@H:32]2[CH2:36][O:35]C(C)(C)[O:33]2)=[CH:26][CH:25]=1)[CH2:8][NH:9][C:10]([C:12]1[C:17]([NH2:18])=[N:16][C:15]([NH2:19])=[C:14]([Cl:20])[N:13]=1)=[O:11].C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:33][C@@H:32]([CH2:36][OH:35])[CH2:31][O:30][C:27]1[CH:26]=[CH:25][C:24]([CH2:23][CH2:22][CH2:21][CH:7]([NH:6][CH2:5][C:4]2[CH:39]=[CH:40][C:41]([O:43][CH3:44])=[CH:42][C:3]=2[O:2][CH3:1])[CH2:8][NH:9][C:10]([C:12]2[C:17]([NH2:18])=[N:16][C:15]([NH2:19])=[C:14]([Cl:20])[N:13]=2)=[O:11])=[CH:29][CH:28]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86651885HCID 86651885, compound

Product 1

HCID 44512786HCID 44512786, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid {2-(2,4-dimethoxy-benzylamino)-5-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-pentyl}-amide (391 mg, 0.62 mmol) in DCM (3 mL) is added TFA (3 mL) and the reaction is stirred at RT for 72 h. The solvent is removed in vacuo and the residue is diluted with water (20 mL) and EtOAc (20 mL). The layers are separated and the aqueous phase is neutralised with aqueous sodium hydroxide and then extracted with EtOAc (2×20 mL). The EtOAc extracts are combined and dried (MgSO4), filtered and the solvent is removed in vacuo. Chromatography (SiO2, MeOH:DCM, 1:9) affords the title compound as a colourless solid as a mixture of diastereoisomers. [M+H]+ 589. 1H NMR (400 MHz, CDCl3) δ 7.63 (1H, br), 7.05 and 7.04 (1H, 2×d), 6.98 and 6.97 (2H, 2×d), 6.73 and 6.71 (2H 2×d), 6.36 and 6.35 (1H, 2×d), 6.34 and 6.30 (1H, 2×s), 5.15 (2H, br), 4.08-3.59 (8H, m), 3.71 (3H, s), 3.65 (3H, s), 3.50-3.41 (2H, m) 2.55 and 2.49 (2H, 2×t), 1.80-1.29 (4H, m).

Workup

  1. customThe solvent is removed in vacuo
  2. additionthe residue is diluted with water (20 mL) and EtOAc (20 mL)
  3. customThe layers are separated
  4. extractionextracted with EtOAc (2×20 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent is removed in vacuo

Sources & evidence

ORD record
ord-9d8d3ffce8aa49f898cabab23ed14d84
Source dataset
uspto-grants-2014_03
Patent number
US08664228B2

Reaction notes

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