Ethylenediamine → HCID 71285853, compound

HRID 246279Notes

Reaction equation

HRID 246279 reaction equation
[F:1][C:2]([F:44])([F:43])[O:3][C:4]1[CH:5]=[C:6]([C@@H:10]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[C:32]5[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=5)[N:26]([CH3:34])[N:25]=4)[N:22]=3)[N:17](COCC[Si](C)(C)C)[CH:16]=2)=[O:14])[CH3:11])[CH:7]=[CH:8][CH:9]=1.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[F:44][C:2]([F:1])([F:43])[O:3][C:4]1[CH:5]=[C:6]([C@@H:10]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[C:32]5[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=5)[N:26]([CH3:34])[N:25]=4)[N:22]=3)[NH:17][CH:16]=2)=[O:14])[CH3:11])[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71288384HCID 71288384, compound

Product 1

HCID 71285853HCID 71285853, compoundYield 57.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 10 ml round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(S)-1-(3-trifluoromethoxy-phenyl)-ethyl]-amide (123 mg, 0.196 mmol) was dissolved in dichloromethane (1 ml) and trifluoroacetic acid (0.6 ml, 7.9 mmol) was added. The light yellow reaction was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (1 ml) and ethylenediamine (0.80 ml, 11.8 mmol) was added. The yellow reaction mixture was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resulting suspension was filtered and washed with hot water and ethyl acetate and the solid collected was dried under high vacuum to provide 56 mg (57%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(S)-1-(3-trifluoromethoxy-phenyl)-ethyl]-amide as a light yellow powder. MS: (M+Na)+=521; 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 12.85 (br. s., 1H), 9.11 (s, 1H), 8.53 (d, J=7.8 Hz, 1H), 8.45 (s, 1H), 8.36 (dd, J=9.2, 5.2 Hz, 1H), 7.67 (dd, J=9.7, 1.9 Hz, 1H), 7.39-7.54 (m, 3H), 7.24 (d, J=7.1 Hz, 1H), 6.98 (td, J=9.0, 2.1 Hz, 1H), 5.27-5.43 (m, 1H), 4.14 (s, 3H), 1.65 (d, J=7.1 Hz, 3H).

Workup

  1. customThe light yellow reaction
  2. concentrationthen concentrated
  3. dissolutionThe residue was dissolved in dichloromethane (1 ml)
  4. stirringThe yellow reaction mixture was stirred at room temperature for 1 h
  5. customthen quenched with water
  6. additiondiluted with ethyl acetate
  7. filtrationThe resulting suspension was filtered
  8. washwashed with hot water and ethyl acetate
  9. customthe solid collected
  10. customwas dried under high vacuum

Sources & evidence

ORD record
ord-6bdf2688169b4a03b96f2a65a0c52b05
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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