Trifluoroacetic acid → 2-(6-chloro-1-ethyl-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 246033Notes

Reaction equation

HRID 246033 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:42])[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]([CH2:32][CH3:33])[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].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([CH:3]1[CH2:4][N:5]([C:7](=[O:42])[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]([CH2:32][CH3:33])[N:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:6]1)#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 712889072-(6-chloro-1-ethyl-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 712860792-(6-chloro-1-ethyl-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 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(6-chloro-1-ethyl-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 (150 mg, 0.25 mmol) in CH2Cl2 (2 mL) was added TFA (0.75 mL). The reaction mixture was stirred at room temperature for 5 h then concentrated. The residue was redissolved in 10:90:0.5 MeOH/CH2Cl2/NH4OH (3 mL) and stirred at room temperature for 3 h. The reaction mixture was concentrated and the residue was purified by silica gel chromatography with 0% to 5% MeOH/EtOAc followed by trituration with MeOH to afford 88 mg (75%) of 2-(6-chloro-1-ethyl-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 white powder. MS: (M+Na)+=499; mp=248-255° C.; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.92 (br. s., 1H), 9.14 (s, 1H), 8.71 (d, J=8.7 Hz, 1H), 8.47 (dd, J=7.6, 3.4 Hz, 2H), 8.02 (s, 1H), 7.25 (d, J=8.7 Hz, 1H), 4.48-4.79 (m, 5H), 4.04-4.28 (m, 2H), 3.77-3.92 (m, 1H), 1.47 (t, J=7.2 Hz, 3H), 1.39 (dd, J=6.8, 4.5 Hz, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in 10:90:0.5 MeOH/CH2Cl2/NH4OH (3 mL)
  3. stirringstirred at room temperature for 3 h
  4. concentrationThe reaction mixture was concentrated
  5. customthe residue was purified by silica gel chromatography with 0% to 5% MeOH/EtOAc

Sources & evidence

ORD record
ord-f7ceb6f9879743c89f6b4dfa1509dee8
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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