Trifluoroacetic acid → 2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246703Notes

Reaction equation

HRID 246703 reaction equation
[Si]([O:8][CH2:9][C:10]([NH:13][C:14]([C:16]1[C:20]2=[N:21][C:22]([C:25]3[C:33]4[C:28](=[CH:29][CH:30]=[C:31]([O:34][CH:35]([F:37])[F:36])[CH:32]=4)[N:27]([CH2:38][CH2:39][CH2:40][N:41]([CH3:43])[CH3:42])[N:26]=3)=[CH:23][N:24]=[C:19]2[N:18](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:17]=1)=[O:15])([CH3:12])[CH3:11])(C(C)(C)C)(C)C.FC(F)(F)C(O)=O>ClCCl>[F:37][CH:35]([F:36])[O:34][C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][CH:30]=1)[N:27]([CH2:38][CH2:39][CH2:40][N:41]([CH3:42])[CH3:43])[N:26]=[C:25]2[C:22]1[N:21]=[C:20]2[C:16]([C:14]([NH:13][C:10]([CH3:11])([CH3:12])[CH2:9][OH:8])=[O:15])=[CH:17][NH:18][C:19]2=[N:24][CH:23]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280050N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Product 1

HCID 712806342-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideYield 36.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the solution of N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (88 mg, 0.12 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-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide as yellow solid (22 mg, 34.5%). LCMS: (M+H)+=502; 1H NMR (300 MHz, CD3OD): δ 9.04 (s, 1H), 8.17 (s, 1H), 8.11 (s, 1H), 7.66 (d, 1H, J=8.7 Hz), 7.35 (d, 1H, J=8.1 Hz), 6.85 (t, 1H, J=74.1 Hz), 4.59 (s, 2H), 3.84 (s, 2H), 3.34-3.32 (m, 2H), 2.89 (s, 6H), 2.44 (s, 2H), 1.64 (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-ac7d61c8672343fe91ce456d86b66eb4
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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