Trifluoroacetic acid → 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-carbamoyl-1-cyclopropyl-2-methyl-propyl)-amide

HRID 446938Notes

Reaction equation

HRID 446938 reaction equation
[C:1]([C:4]([CH3:33])([CH3:32])[CH:5]([NH:9][C:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([CH:21]3[CH2:23][CH2:22]3)[N:19]=2)[N:14](COCC[Si](C)(C)C)[CH:13]=1)=[O:11])[CH:6]1[CH2:8][CH2:7]1)(=[O:3])[NH2:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([C:4]([CH3:33])([CH3:32])[CH:5]([NH:9][C:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([CH:21]3[CH2:22][CH2:23]3)[N:19]=2)[NH:14][CH:13]=1)=[O:11])[CH:6]1[CH2:7][CH2:8]1)(=[O:3])[NH2:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 673888952-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-carbamoyl-1-cyclopropyl-2-methyl-propyl)-amide

Product 1

HCID 533898212-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-carbamoyl-1-cyclopropyl-2-methyl-propyl)-amideYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-carbamoyl-1-cyclopropyl-2-methyl-propyl)-amide (108 mg, 0.23 mmol) in CH2Cl2 (4 mL) was added TFA (1 mL). The yellow reaction mixture was stirred 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 for 1 h then concentrated. The residue was purified by SiO2 chromatography (50% to 100% EtOAc/hexanes to 5% MeOH/EtOAc) followed by trituration with Et2O to afford 44 mg (56%) of 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-carbamoyl-1-cyclopropyl-2-methyl-propyl)-amide as a white solid. MS: (M+H)+=342; mp=222.0-224.0.

Workup

  1. concentrationthen concentrated The residue
  2. dissolutionwas redissolved in CH2Cl2 (4 ml)
  3. additionethylenediamine (0.5 mL) was added
  4. stirringThe reaction mixture was stirred for 1 h
  5. concentrationthen concentrated
  6. customThe residue was purified by SiO2 chromatography (50% to 100% EtOAc/hexanes to 5% MeOH/EtOAc)

Sources & evidence

ORD record
ord-15d8b85418444e389029f0c698c88916
Source dataset
uspto-grants-2013_07
Patent number
US08481541B2

Reaction notes

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