Ethylenediamine → 2-(6-chloro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

HRID 245835Notes

Reaction equation

HRID 245835 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:40])[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)[NH:24][N: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[CH2:4][N:5]([C:7](=[O:40])[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)[NH:24][N:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:6]1)#[N:2]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712888432-(6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-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 712886852-(6-chloro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amideYield 59.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a round-bottomed flask, 2-(6-chloro-1H-indazol-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 (65 mg, 0.112 mmol) was dissolved in dichloromethane (0.6 ml) and trifluoroacetic acid (0.35 ml, 4.5 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was redissolved in dichloromethane (0.6 ml) and ethylenediamine (0.46 ml, 6.8 mmol) was added. The solution was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resultant suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 30 mg (59%) of 2-(6-chloro-1H-indazol-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 light yellow powder. MS: (M+H)+=449.

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in dichloromethane (0.6 ml)
  3. stirringThe solution was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resultant suspension was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-640516f4f6be44c68fd105ffb9f881e2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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