Trifluoroacetic acid → HCID 71279672, compound

HRID 246726Notes

Reaction equation

HRID 246726 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][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[N:19]([CH2:30][CH2:31][CH:32]4[CH2:36][O:35]C(C)(C)[O:33]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][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[N:19]([CH2:30][CH2:31][CH:32]([OH:33])[CH2:36][OH:35])[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 71280145N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Product 1

HCID 71279672HCID 71279672, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide in dichloromethane (2 mL) was added drop-wise trifluoroacetic acid (1 mL) at room temperature and the reaction mixture was stirred for 2 hours. The solvent was removed 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: 38% acetonitrile/62% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 46% acetonitrile/54% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(3,4-dihydroxybutyl)-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (30 mg, 39% over two steps) as a white solid. MS: (M+H)+=489.1; 1H NMR (300 MHz, DMSO): δ 12.85 (s, 1H), 9.11 (s, 1H), 8.42 (d, 1H, J=3.0 Hz), 8.24 (d, 1H, J=1.2 Hz), 7.92-7.88 (m, 2H), 7.45 (t, 1H, J=9.2 Hz), 7.23 (t, 1H, J=74.4 Hz), 4.67-4.64 (m, 2H), 3.48-3.26 (m, 4H), 2.16-2.10 (m, 4H), 1.86-1.83 (m, 4H), 1.54 (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. wait38% acetonitrile/62% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 46% acetonitrile/54% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

Sources & evidence

ORD record
ord-e9e1603d92074fc7818e4361e8928712
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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