Trifluoroacetic acid → HCID 67386009, compound

HRID 1898617Notes

Reaction equation

HRID 1898617 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:42])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28](=[O:33])[NH:29][CH:30]([CH3:32])[CH3:31])[CH:23]=4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:42])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28](=[O:33])[NH:29][CH:30]([CH3:31])[CH3:32])[CH:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67386587HCID 67386587, compound

Product 1

HCID 67386009HCID 67386009, compoundYield 74.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(3-isopropylcarbamoyl-phenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (52 mg, 0.088 mmol) in CH2Cl2 (4 mL) was added TFA (1.5 mL). The reaction mixture was stirred at room temp for 3 h then concentrated. The residue was redissolved in CH2Cl2 (4 mL) and ethylenediamine (0.5 mL) was added. The reaction mixture was stirred at room temp for 0.5 h then concentrated. The residue was purified by silica gel chromatography (50% to 100% EtOAc/hexanes to 5% MeOH) then triturated with Et2O to isolate 30 mg (70%) of 2-(3-isopropylcarbamoyl-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a white powder. MS: (M+H)+=460.

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in CH2Cl2 (4 mL)
  3. additionethylenediamine (0.5 mL) was added
  4. stirringThe reaction mixture was stirred at room temp for 0.5 h
  5. concentrationthen concentrated
  6. customThe residue was purified by silica gel chromatography (50% to 100% EtOAc/hexanes to 5% MeOH)
  7. customthen triturated with Et2O

Sources & evidence

ORD record
ord-6b119972cbd84d6fb8348c09c7e31d38
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

Loading…