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

HRID 246682Notes

Reaction equation

HRID 246682 reaction equation
[CH3:1][C:2]1([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:26]4[C:34]5[C:29](=[CH:30][C:31]([CH3:35])=[CH:32][CH:33]=5)[NH:28][N:27]=4)[N:24]=3)[NH:19][CH:18]=2)=[O:16])[CH2:6][CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.[F:36][C:37]([F:42])([F:41])[C:38]([OH:40])=[O:39]>ClCCl>[F:36][C:37]([F:42])([F:41])[C:38]([OH:40])=[O:39].[CH3:35][C:31]1[CH:30]=[C:29]2[C:34]([C:26]([C:23]3[N:24]=[C:25]4[C:17]([C:15]([NH:14][C:2]5([CH3:1])[CH2:6][CH2:5][NH:4][CH2:3]5)=[O:16])=[CH:18][NH:19][C:20]4=[N:21][CH:22]=3)=[N:27][NH:28]2)=[CH:33][CH:32]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71279771tert-butyl 3-methyl-3-(2-(6-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)pyrrolidine-1-carboxylate

Product 1

HCID 712801782-(6-methyl-1H-indazol-3-yl)-N-(3-methylpyrrolidin-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide 2,2,2-trifluoroacetateYield 22.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 3-methyl-3-(2-(6-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)pyrrolidine-1-carboxylate (76 mg, 0.16 mmol) in 6 mL of dichloromethane was added trifluoroacetic acid (3 mL) in one portion at room temperature and 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 45% acetonitrile/65% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-methyl-1H-indazol-3-yl)-N-(3-methylpyrrolidin-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide 2,2,2-trifluoroacetate (18 mg, 22.9%) as a white solid. MS: (M+H)+=376; 1H NMR (300 MHz, DMSO): δ 13.43 (s, 1H), 9.17 (s, 1H), 8.80 (brs, 1H), 8.49 (s, 1H), 8.38 (d, 1H, J=8.1 Hz), 8.29 (s, 1H), 7.47 (s, 1H), 7.16 (d, 1H, J=8.4 Hz), 3.94 (d, 1H, J=12.0 Hz), 3.51-3.20 (m, 3H), 2.57 (s, 3H), 2.30-2.17 (m, 2H), 1.70 (s, 3H).

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 45% acetonitrile/65% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

Sources & evidence

ORD record
ord-f528b14465e8450d8bda38b0d7179999
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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