Trifluoroacetic acid → HCID 71285901, compound

HRID 246225Notes

Reaction equation

HRID 246225 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2([NH:12][C:13]([C:15]3[C:23]4[C:18](=[N:19][CH:20]=[C:21]([C:24]5[C:32]6[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=6)[N:26]([CH3:34])[N:25]=5)[N:22]=4)[N:17](COCC[Si](C)(C)C)[CH:16]=3)=[O:14])[CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C(O)(C(F)(F)F)=O.CC(=O)OCC.C(N(CC)CC)C>ClCCl.CO>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2([NH:12][C:13]([C:15]3[C:23]4[C:18](=[N:19][CH:20]=[C:21]([C:24]5[C:32]6[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=6)[N:26]([CH3:34])[N:25]=5)[N:22]=4)[NH:17][CH:16]=3)=[O:14])[CH2:9][CH2:10][CH2:11]2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 71285950HCID 71285950, compound

Product 1

HCID 71285901HCID 71285901, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a light brown solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(3-bromo-phenyl)-cyclobutyl]-amide (50 mg, 0.077 mmol) in dichloromethane (3 mL) was added an excess of TFA (1.2 mL, 15.4 mmol) at room temperature under nitrogen atmosphere. The resulting light brown solution was stirred for 4 h at which time TLC analysis (EA, Rf=0.35) indicated the absence of starting material. Then, the solvent was removed under vacuum and the residue was azeotroped with toluene to obtain a light brown solid. Then, this solid was treated with an excess of triethylamine (1.07 mL, 7.7 mmol) in methanol (3 mL) at room temperature under nitrogen atmosphere. The resulting suspension was stirred for 15 h and then the solvent was removed under vacuum. The residue was triturated with acetonitrile and the solids were collected by filtration and washed with acetonitrile. After drying in air, 15 mg (38%) of the 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(3-bromo-phenyl)-cyclobutyl]-amide was isolated as a light yellow solid. LC-MS (M+H)+=519; 1H NMR (300 MHz, DMSO-d6) δ: 12.80 (br. s., 1H), 9.10 (s, 1H), 8.77 (s, 1H), 8.55 (dd, J=8.8, 5.5 Hz, 1H), 8.36 (s, 1H), 7.64-7.80 (m, 2H), 7.57 (d, J=7.8 Hz, 1H), 7.41 (d, J=7.8 Hz, 1H), 7.23-7.35 (m, 1H), 7.15 (t, J=8.2 Hz, 1H), 4.15 (s, 3H), 2.56-2.81 (m, 4H), 2.19 (d, J=8.5 Hz, 1H), 1.96 (d, J=8.3 Hz, 1H).

Workup

  1. customThen, the solvent was removed under vacuum
  2. customthe residue was azeotroped with toluene
  3. customto obtain a light brown solid
  4. customthe solvent was removed under vacuum
  5. customThe residue was triturated with acetonitrile
  6. filtrationthe solids were collected by filtration
  7. washwashed with acetonitrile
  8. customAfter drying in air

Sources & evidence

ORD record
ord-001c211d453143d7b80ce59d66300937
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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