Ethylenediamine → 2-(6-chloro-1-methylindol-3-yl)-N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 245840Notes

Reaction equation

HRID 245840 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:41])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[CH:23]=4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:41])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[CH:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712861872-(6-chloro-1-methyl-1H-indol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

Product 1

HCID 712886932-(6-chloro-1-methylindol-3-yl)-N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 66.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a round-bottomed flask, 2-(6-chloro-1-methyl-1H-indol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (54 mg, 0.091 mmol) was dissolved in dichloromethane (0.5 ml) and trifluoroacetic acid (0.28 ml, 3.63 mmol) was added. The dark red solution was stirred at room temperature for 2 h then concentrated. The residue was redissolved in dichloromethane (0.5 ml) and ethylenediamine (0.37 ml, 5.48 mmol) was added. The reaction mixture 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 28 mg (63%) of 2-(6-chloro-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a yellow powder.

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in dichloromethane (0.5 ml)
  3. stirringThe reaction mixture 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-a871f75a1d5542a4aca404567010a087
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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