Trifluoroacetic acid → 2-(6-tert-butyl-1-methylindazol-3-yl)-N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246029Notes

Reaction equation

HRID 246029 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:44])[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]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:28][CH:29]=5)[N:24]([CH3:35])[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:44])[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]([C:31]([CH3:33])([CH3:32])[CH3:34])=[CH:28][CH:29]=5)[N:24]([CH3:35])[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 712889062-(6-tert-butyl-1-methyl-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 712861842-(6-tert-butyl-1-methylindazol-3-yl)-N-[(2R)-1-(3-cyanoazetidin-1-yl)-1-oxopropan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(6-tert-butyl-1-methyl-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 (129 mg, 0.21 mmol) in CH2Cl2 (2 mL) was added TFA (0.75 mL). The reaction mixture was stirred at room temperature for 4 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 to afford 74 mg (73%) of 2-(6-tert-butyl-1-methyl-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)+=485; mp=180-195° C.; 1H NMR (CDCl3, 400 MHz): δ (ppm) 10.08-10.28 (m, 1H), 9.02-9.14 (m, 1H), 8.65 (d, J=7.1 Hz, 1H), 8.46 (d, J=8.6 Hz, 1H), 7.99-8.13 (m, 1H), 7.40-7.49 (m, 1H), 7.36 (s, 1H), 4.86-5.08 (m, 1H), 4.23-4.76 (m, 4H), 4.11 (s, 3H), 3.52-3.59 (m, 1H), 1.55-1.71 (m, 3H), 1.48 (s, 9H).

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-7b640901ef54469192f1dfbcbd3504b4
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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