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

HRID 245889Notes

Reaction equation

HRID 245889 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][C@H:4]([NH:7][C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[C:27]5[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=5)[N:21]([CH3:29])[N:20]=4)[N:17]=3)[N:12](COCC[Si](C)(C)C)[CH:11]=2)=[O:9])[CH2:3]1.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[OH:1][C@@H:2]1[CH2:6][CH2:5][C@H:4]([NH:7][C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[C:27]5[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=5)[N:21]([CH3:29])[N:20]=4)[N:17]=3)[NH:12][CH:11]=2)=[O:9])[CH2:3]1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712882622-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-hydroxy-cyclopentyl)-amide

Product 1

HCID 712882642-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-hydroxy-cyclopentyl)-amideYield 79.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-hydroxy-cyclopentyl)-amide (49 mg, 0.093 mmol) was dissolved in dichloromethane (0.5 ml) and trifluoroacetic acid (0.3 ml, 3.8 mmol) was added. The orange reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.5 ml) and ethylenediamine (0.4 ml, 5.7 mmol) was added. The light yellow solution was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resulting precipitate was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 29 mg (75%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-hydroxy-cyclopentyl)-amide as an off-white powder. MS: (M+H)+=395; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.42 (br. s., 1H), 9.11 (s, 1H), 8.59 (dd, J=9.1, 5.3 Hz, 1H), 8.42 (s, 1H), 8.20 (d, J=8.3 Hz, 1H), 7.68 (dd, J=9.6, 2.1 Hz, 1H), 7.24 (td, J=9.2, 2.1 Hz, 1H), 4.78 (br. s., 1H), 4.36-4.52 (m, 1H), 4.22 (br. s., 1H), 4.15 (s, 3H), 2.30 (ddd, J=13.7, 8.2, 5.7 Hz, 1H), 2.04-2.19 (m, 1H), 1.67-1.86 (m, 3H), 1.49-1.63 (m, 1H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.5 ml)
  3. stirringThe light yellow solution was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resulting precipitate was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-0459653e7ede408290608a6b6133853d
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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