Trifluoroacetic acid → N-(1-methylcyclopropyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide trifluoroacetate

HRID 246748Notes

Reaction equation

HRID 246748 reaction equation
FC(F)OC1C=C2C(=CC=1)N(CCCN(C)C)N=C2[C:19]1[N:24]=[C:23]2[C:25]([C:47]([NH:49][C:50]3([CH3:53])[CH2:52][CH2:51]3)=[O:48])=[CH:26][N:27](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:22]2=[N:21][CH:20]=1.[F:55][C:56]([F:61])([F:60])[C:57]([OH:59])=[O:58]>ClCCl>[F:55][C:56]([F:61])([F:60])[C:57]([OH:59])=[O:58].[CH3:53][C:50]1([NH:49][C:47]([C:25]2[C:23]3=[N:24][CH:19]=[CH:20][N:21]=[C:22]3[NH:27][CH:26]=2)=[O:48])[CH2:51][CH2:52]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 712806692-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-N-(1-methylcyclopropyl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Product 1

HCID 86678013N-(1-methylcyclopropyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide trifluoroacetateYield 7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-N-(1-methylcyclopropyl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (200 mg, 0.3 mmol) in 3 mL of dichloromethane was added trifluoroacetic acid (3 mL). The reaction mixture was stirred at room temperature overnight. After solvent evaporation, 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 are: 40% acetonitrile/60% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min) to afford 245-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-N-(1-methylcyclopropyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide trifluoroacetate (20 mg, 7%) as a yellow solid. LCMS: (M+H)+=484; 1H NMR (300 MHz, CD3OD): δ 9.04 (s, 1H), 8.13 (s, 1H), 8.02 (s, 1H), 7.61 (d, 1H, J=9.0 Hz), 7.29 (dd, 1H, J1=9.0 Hz, J2=2.1 Hz), 6.78 (t, 1H, J=73.8 Hz), 4.56-4.52 (m, 2H), 3.19-3.12 (m, 2H), 2.79 (s, 6H), 2.39-2.33 (m, 2H), 1.47 (s, 3H), 0.93-0.89 (m, 2H), 0.76-0.72 (m, 2H).

Workup

  1. customAfter solvent evaporation
  2. customthe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait40% acetonitrile/60% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min

Sources & evidence

ORD record
ord-d8eb6f916f0347e1acdc1e23e2ec0001
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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