Trifluoroacetic acid → N-(4-amino-2-methylbutan-2-yl)-2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide 2,2,2-trifluoroacetate

HRID 246648Notes

Reaction equation

HRID 246648 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:23][C:24]([CH3:36])([CH3:35])[CH2:25][CH2:26][NH:27]C(=O)OC(C)(C)C)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[F:37][C:38]([F:43])([F:42])[C:39]([OH:41])=[O:40]>ClCCl>[F:37][C:38]([F:43])([F:42])[C:39]([OH:41])=[O:40].[NH2:27][CH2:26][CH2:25][C:24]([NH:23][C:21]([C:20]1[C:14]2[C:15](=[N:16][CH:17]=[C:12]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=4)[N:8]([CH3:11])[N:7]=3)[N:13]=2)[NH:18][CH:19]=1)=[O:22])([CH3:35])[CH3:36]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280317tert-butyl 3-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-3-methylbutylcarbamate

Product 1

HCID 71280032N-(4-amino-2-methylbutan-2-yl)-2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide 2,2,2-trifluoroacetateYield 30.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 3-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-3-methylbutylcarbamate (110 mg, 0.22 mmol) in 6 mL of dichloromethane was added trifluoroacetic acid (3 mL) in one portion at room temperature and the solution stirred for one hour. The solvent was evaporated at 40° C. under reduced pressure and the residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 20% acetonitrile/80% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 50% acetonitrile/50% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give N-(4-amino-2-methylbutan-2-yl)-2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide 2,2,2-trifluoroacetate (35 mg, 30.9%) as a yellow solid. MS: (M+H)+=396; 1H NMR (300 MHz, DMSO): δ 12.94 (s, 1H), 9.11 (s, 1H), 8.50-8.43 (m, 2H), 7.89 (s, 1H), 7.74-7.70 (m, 3H), 7.70-7.21 (m, 1H), 4.18 (s, 3H), 2.90 (brs, 2H), 2.31-2.26 (m, 2H), 1.53 (s, 6H).

Workup

  1. customThe solvent was evaporated at 40° C. under reduced pressure
  2. customthe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait20% acetonitrile/80% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 50% acetonitrile/50% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

Sources & evidence

ORD record
ord-007adab7be334371ac77621d186ae65c
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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