Trifluoroacetic acid → 2-[6-chloro-1-propyl-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 246043Notes

Reaction equation

HRID 246043 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:43])[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][CH2:33][CH3:34])[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:43])[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][CH2:33][CH3:34])[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 712861762-(6-chloro-1-propyl-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 712885722-[6-chloro-1-propyl-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 33.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(6-chloro-1-propyl-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 (38 mg, 0.06 mmol) in CH2Cl2 (1.5 mL) was added TFA (0.5 mL). The reaction mixture was stirred at room temperature for 3 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 10% MeOH/CH2Cl2 to afford 10 mg (32%) of 2-[6-chloro-1-propyl-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 solid. MS: (M+Na)+=513; mp=219-221° C.; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.93 (s, 1H), 9.13 (s, 1H), 8.71 (d, J=9.1 Hz, 1H), 8.46 (dd, J=7.6, 2.6 Hz, 2H), 8.03 (s, 1H), 7.25 (d, J=9.1 Hz, 1H), 4.43-4.78 (m, 5H), 4.16-4.27 (m, 1H), 4.05-4.13 (m, 1H), 3.78-3.91 (m, 1H), 1.86-1.96 (m, 2H), 1.39 (dd, J=6.6, 4.3 Hz, 3H), 0.89 (t, J=7.4 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 10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-0bc232d6673f43db887e62ba82fca8e9
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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