Ethylenediamine → HCID 71285651, compound

HRID 246282Notes

Reaction equation

HRID 246282 reaction equation
[OH:1][C:2]([C:5]1([NH:9][C:10]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[C:29]5[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=5)[N:23]([CH3:31])[N:22]=4)[N:19]=3)[N:14](COCC[Si](C)(C)C)[CH:13]=2)=[O:11])[CH2:8][CH2:7][CH2:6]1)([CH3:4])[CH3:3].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[OH:1][C:2]([C:5]1([NH:9][C:10]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[C:29]5[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=5)[N:23]([CH3:31])[N:22]=4)[N:19]=3)[NH:14][CH:13]=2)=[O:11])[CH2:6][CH2:7][CH2:8]1)([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71285812HCID 71285812, compound

Product 1

HCID 71285651HCID 71285651, compoundYield 66.1%

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 [1-(1-hydroxy-1-methyl-ethyl)-cyclobutyl]-amide (140 mg, 0.24 mmol) was dissolved in dichloromethane (1.2 ml) and trifluoroacetic acid (0.75 ml, 9.7 mmol) was added. The orange reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was dissolved in dichloromethane (1.2 ml) and ethylenediamine (1.0 ml, 14.8 mmol) was added. The reaction 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 then dried under high vacuum to provide 67 mg (63%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(1-hydroxy-1-methyl-ethyl)-cyclobutyl]-amide as a light yellow powder. MS: (M+Na)+=445; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.11 (s, 1H), 8.53 (dd, J=8.9, 5.5 Hz, 1H), 8.41 (s, 1H), 8.31 (s, 1H), 7.68 (dd, J=9.8, 2.3 Hz, 1H), 7.08-7.23 (m, 1H), 4.99 (br. s., 1H), 4.15 (s, 3H), 2.38-2.62 (m, 4H), 1.84-2.02 (m, 1H), 1.66-1.83 (m, 1H), 1.23 (s, 6H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (1.2 ml)
  3. stirringThe reaction 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. customthen dried under high vacuum

Sources & evidence

ORD record
ord-7436e08c6c0e43eeae5c2b31d56ec6d8
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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