Ethylenediamine → 2-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide

HRID 246266Notes

Reaction equation

HRID 246266 reaction equation
[CH3:1][CH:2]([NH:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[N:24]([CH2:32][CH2:33][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)[N:23]=3)[N:20]=2)[N:15](COCC[Si](C)(C)C)[CH:14]=1)=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][CH:2]([NH:10][C:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:22]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[N:24]([CH2:32][CH2:33][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)[N:23]=3)[N:20]=2)[NH:15][CH:14]=1)=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712883782-[6-Fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)amide

Product 1

HCID 712883822-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amideYield 43.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[6-Fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)amide (75 mg, 0.117 mmol) was combined with dichloromethane (1 mL) then trifluoroacetic acid (0.26 ml, 3.50 mmol) was added. After stirring for 2 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (1 mL) and ethylenediamine (0.23 ml, 3.50 mmol) was added and the reaction was stirred at room temperature for 20 min. The reaction mixture was concentrated in vacuo and the residue was triturated with water (2 mL). The precipitate was filtered, washed with water and dried to afford 26 mg (41%) of 2-[6-fluoro-1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide (26 mg, 41%) as a yellow solid. MS: (M+H)+=513; 1H NMR (DMSO-d6) δ: 9.07 (s, 1H), 8.32-8.44 (m, 2H), 8.22 (d, J=8.3 Hz, 1H), 7.73 (d, J=9.8 Hz, 1H), 7.50-7.66 (m, 2H), 7.27 (d, J=7.8 Hz, 1H), 7.03-7.16 (m, 2H), 4.53-4.67 (m, 4H), 4.46 (s, 1H), 3.02-3.25 (m, 2H), 2.98 (t, J=6.5 Hz, 3H), 1.64 (br. s., 5H), 1.29 (d, J=6.5 Hz, 3H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (1 mL)
  3. stirringthe reaction was stirred at room temperature for 20 min
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe residue was triturated with water (2 mL)
  6. filtrationThe precipitate was filtered
  7. washwashed with water
  8. customdried

Sources & evidence

ORD record
ord-7594e4ca97c74bc09894f3a4ecb8b896
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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