Ethylenediamine → 2-(6,8-difluoro-imidazo[1,5-a]pyridin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

HRID 245871Notes

Reaction equation

HRID 245871 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[N:19]=[CH:20][N:21]4[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[C:22]=34)[N:16]=2)[N:11](COCC[Si](C)(C)C)[CH:10]=1)=[O:8])[CH3:5].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[N:19]=[CH:20][N:21]4[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[C:22]=34)[N:16]=2)[NH:11][CH:10]=1)=[O:8])[CH3:5]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712881892-(6,8-difluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

Product 1

HCID 712881832-(6,8-difluoro-imidazo[1,5-a]pyridin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amideYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a round-bottomed flask, 2-(6,8-difluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide (134 mg, 0.25 mmol) was dissolved in dichloromethane (1.2 ml) and trifluoroacetic acid (0.75 ml, 9.8 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (1.2 ml) and ethylenediamine (1.0 ml, 14.8 mmol) was added. The yellow solution was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resulting suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 74 mg (78%) of 2-(6,8-difluoro-imidazo[1,5-a]pyridin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a yellow powder. MS: (M+H)+=387; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.14 (br. s., 1H), 9.03 (s, 1H), 8.70 (d, J=1.9 Hz, 1H), 8.63 (dd, J=4.2, 1.9 Hz, 1H), 8.37 (s, 1H), 8.29 (d, J=8.3 Hz, 1H), 7.24-7.36 (m, 1H), 4.32 (dt, J=13.2, 6.6 Hz, 1H), 3.42-3.51 (m, 1H), 3.35-3.41 (m, 1H), 3.25 (s, 3H), 1.24 (d, J=6.8 Hz, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (1.2 ml)
  3. stirringThe yellow solution was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resulting suspension was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-ce14de63157240068a02ffdeaf6e6d29
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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