Trifluoroacetic acid → HCID 71288774, compound

HRID 246059Notes

Reaction equation

HRID 246059 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:39])[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:23]5[S:30][CH:29]=[CH:28][C:24]=5[N:25]([CH3:27])[N:26]=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:39])[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:23]5[S:30][CH:29]=[CH:28][C:24]=5[N:25]([CH3:27])[N:26]=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 71288910HCID 71288910, compound

Product 1

HCID 71288774HCID 71288774, compoundYield 83.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(1-methyl-1H-thieno[3,2-c]pyrazol-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 (131 mg, 0.23 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 10% MeOH/CH2Cl2 to afford 83 mg (83%) of 2-(1-methyl-1H-thieno[3,2-c]pyrazol-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)+=457; mp=310-320° C.; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.93 (br. s., 1H), 9.07 (s, 1H), 8.46 (d, J=11.0 Hz, 1H), 8.19 (d, J=7.9 Hz, 1H), 7.82 (d, J=5.3 Hz, 1H), 7.32 (d, J=5.3 Hz, 1H), 4.42-4.77 (m, 3H), 4.13-4.21 (m, 1H), 4.12 (s, 3H), 3.97-4.08 (m, 1H), 3.76-3.89 (m, 1H), 1.51 (dd, J=6.8, 2.6 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-8bae6394591b4b3c951d83d82527de2a
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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