Ethylenediamine → HCID 71288172, compound

HRID 245935Notes

Reaction equation

HRID 245935 reaction equation
FC(F)(F)C(O)=O.C(N)CN.[F:12][C:13]([F:54])([CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C@H:14]([NH:16][C:17]([C:19]1[C:27]2[C:22](=[N:23][CH:24]=[C:25]([C:28]3[C:36]4[C:31](=[CH:32][C:33]([F:37])=[CH:34][CH:35]=4)[N:30]([CH3:38])[N:29]=3)[N:26]=2)[N:21](COCC[Si](C)(C)C)[CH:20]=1)=[O:18])[CH3:15]>ClCCl>[F:54][C:13]([F:12])([CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C@H:14]([NH:16][C:17]([C:19]1[C:27]2[C:22](=[N:23][CH:24]=[C:25]([C:28]3[C:36]4[C:31](=[CH:32][C:33]([F:37])=[CH:34][CH:35]=4)[N:30]([CH3:38])[N:29]=3)[N:26]=2)[NH:21][CH:20]=1)=[O:18])[CH3:15]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712860172-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2,2-difluoro-1-methyl-3-phenyl-propyl)-amide

Product 1

HCID 71288172HCID 71288172, compoundYield 70%

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 ((R)-2,2-difluoro-1-methyl-3-phenyl-propyl)-amide (133 mg, 0.21 mmol was dissolved in dichloromethane (1.1 ml) and trifluoroacetic acid (0.64 ml, 8.3 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (1.1 ml) and ethylenediamine (0.84 ml, 12.4 mmol) was added. The yellow solution was stirred at room temperature for 1 h then quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was triturated with 5% EtOAc/diethyl ether to afford 73 mg (70%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2,2-difluoro-1-methyl-3-phenyl-propyl)-amide as a light yellow powder. MS: (M+Na)+=501; 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 12.94 (br. s., 1H), 9.12 (s, 1H), 8.52 (s, 1H), 8.47 (dd, J=8.9, 5.4 Hz, 1H), 8.36 (d, J=9.8 Hz, 1H), 7.68 (dd, J=9.8, 2.0 Hz, 1H), 7.23-7.35 (m, 5H), 7.02 (td, J=9.0, 2.3 Hz, 1H), 4.60-4.78 (m, 1H), 4.15 (s, 3H), 3.33-3.45 (m, 2H), 1.41 (d, J=7.0 Hz, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (1.1 ml)
  3. stirringThe yellow solution was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialthen dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was triturated with 5% EtOAc/diethyl ether

Sources & evidence

ORD record
ord-638d590e4617472a99135aa2fd1e3e4f
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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