Trifluoroacetic acid → HCID 71280197, compound

HRID 246753Notes

Reaction equation

HRID 246753 reaction equation
[NH2:1][C:2]([CH3:55])([CH3:54])[CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH:16]([F:18])[F:17])=[CH:12][CH:13]=2)[C:8]([C:19]2[N:24]=[C:23]3[C:25]([C:47]([NH:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])=[CH:26][N:27](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[C:22]3=[N:21][CH:20]=2)=[N:7]1.[F:56][C:57]([F:62])([F:61])[C:58]([OH:60])=[O:59]>ClCCl>[F:56][C:57]([F:62])([F:61])[C:58]([OH:60])=[O:59].[NH2:1][C:2]([CH3:55])([CH3:54])[CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH:16]([F:18])[F:17])=[CH:12][CH:13]=2)[C:8]([C:19]2[N:24]=[C:23]3[C:25]([C:47]([NH:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])=[CH:26][NH:27][C:22]3=[N:21][CH:20]=2)=[N:7]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280139HCID 71280139, compound

Product 1

HCID 71280197HCID 71280197, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(1-(4-amino-4-methylpentyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (54 mg, 0.08 mmol) in 3 mL of dichloromethane was added 3 mL of trifluoroacetic acid. The reaction mixture was stirred overnight at room temperature. 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-(1-(4-amino-4-methylpentyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide 2,2,2-trifluoroacetate (13 mg, 34%) as yellow solid. LCMS: (M+H)+=500; 1H NMR (300 MHz, CD3OD): δ 8.98 (s, 1H), 8.13 (s, 1H), 8.07 (d, 1H, J=2.1 Hz), 7.60 (d, 1H, J=9.3 Hz), 7.29 (dd, 1H, J1=8.7 Hz, J2=2.1 Hz), 6.72 (t, 1H, J=74.1 Hz), 4.49-4.47 (m, 2H), 2.03-1.98 (m, 2H), 1.58-1.53 (m, 2H), 1.49 (s, 9H), 1.19 (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-b17beefa91d946a8ac9f9f47fe8f1a46
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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