Trifluoroacetic acid → N-tert-butyl-2-(1-(3,4-dihydroxybutyl)-6-fluoro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246756Notes

Reaction equation

HRID 246756 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:12]2=[N:13][C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]([CH2:27][CH2:28][CH:29]4[CH2:33][O:32]C(C)(C)[O:30]4)[N:18]=3)=[CH:15][N:16]=[C:11]2[N:10](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([NH:5][C:6]([C:8]1[C:12]2=[N:13][C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]([CH2:27][CH2:28][CH:29]([OH:30])[CH2:33][OH:32])[N:18]=3)=[CH:15][N:16]=[C:11]2[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71279519N-tert-butyl-2-(1-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)-6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Product 1

HCID 71279543N-tert-butyl-2-(1-(3,4-dihydroxybutyl)-6-fluoro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideYield 54.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(1-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)-6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (90 mg, 0.125 mmol) in dichloromethane (2 mL) was added drop-wise trifluoroacetic acid (2 mL) at room temperature and the reaction mixture was stirred for 2 hours. The solvent was removed under reduced pressure. 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: 30% acetonitrile/70% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.) to give N-tert-butyl-2-(1-(3,4-dihydroxybutyl)-6-fluoro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (30 mg, 54.5%) as a white solid. LCMS: (M+H)+=441, (M+Na)+=463; 1H NMR (300 MHz, DMSO): δ12.81 (s, 1H), 9.06 (s, 1H), 8.47-8.42 (m, 1H), 8.37 (s, 1H), 7.91 (s, 1H), 7.64 (d, 1H, J=9.9 Hz), 7.14 (dd, 1H, J1=9.0 Hz, J2=1.8 Hz), 4.57 (t, 2H, J=6.5 Hz), 3.46-3.24 (m, 5H), 2.10-2.08 (m, 1H), 2.06-1.77 (m, 1H), 1.51 (s, 9H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait30% acetonitrile/70% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.

Sources & evidence

ORD record
ord-d260dfcd9ffc44adae913655f6b1fd22
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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