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

HRID 246738Notes

Reaction equation

HRID 246738 reaction equation
[NH2:1][C:2]([CH3:53])([CH3:52])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH3:16])[N:11]=[C:10]2[C:17]1[N:22]=[C:21]2[C:23]([C:45]([NH:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])=[CH:24][N:25](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:20]2=[N:19][CH:18]=1.[F:54][C:55]([F:60])([F:59])[C:56]([OH:58])=[O:57]>ClCCl>[F:54][C:55]([F:60])([F:59])[C:56]([OH:58])=[O:57].[NH2:1][C:2]([CH3:53])([CH3:52])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH3:16])[N:11]=[C:10]2[C:17]1[N:22]=[C:21]2[C:23]([C:45]([NH:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])=[CH:24][NH:25][C:20]2=[N:19][CH:18]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 712794972-(5-(4-amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Product 1

HCID 712805342-(5-(4-amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-N-tert-butyl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide 2,2,2-trifluoroacetateYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-(5-(4-amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (88 mg, 0.12 mmol) in 3 mL of dichloromethane was added trifluoroacetic acid (3 mL). The reaction mixture was stirred overnight at 25° C. 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 2-(5-(4-amino-4-methylpentyloxy)-1-methyl-1H-indazol-3-yl)-N-tert-butyl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide 2,2,2-trifluoroacetate as yellow solid (9 mg, 13%). LCMS: (M+H)+=464; 1H NMR (300 MHz, CD3OD): δ 9.01 (s, 1H), 8.26 (s, 1H), 7.85 (s, 1H), 7.56 (d, 1H, J=9.0 Hz), 7.24 (dd, 1H, J1=9.0 Hz, J2=2.4 Hz), 4.15-4.12 (m, 5H), 1.87-1.84 (m, 4H), 1.59 (s, 9H), 1.27 (s, 6H).

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-9b12733596574866903723d0684adb8c
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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