Trifluoroacetic acid → 2-(6-fluoro-1-(3-(methylsulfonyl)propyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246784Notes

Reaction equation

HRID 246784 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][C:30]([F:34])=[CH:31][CH:32]=4)[N:27]([CH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:40])=[O:39])[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>C(Cl)Cl>[F:34][C:30]1[CH:29]=[C:28]2[C:33]([C:25]([C:22]3[N:21]=[C:20]4[C:16]([C:14]([NH:13][C:10]([CH3:12])([CH3:11])[CH2:9][OH:8])=[O:15])=[CH:17][NH:18][C:19]4=[N:24][CH:23]=3)=[N:26][N:27]2[CH2:35][CH2:36][CH2:37][S:38]([CH3:41])(=[O:40])=[O:39])=[CH:32][CH:31]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280329N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1-(3-(methylsulfonyl)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Product 1

HCID 712795072-(6-fluoro-1-(3-(methylsulfonyl)propyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1-(3-(methylsulfonyl)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (35 mg, 0.042 mmol) in DCM (2 mL) was added trifluoroacetic acid (1 mL) dropwise at room temperature. The reaction mixture was stirred at room temperature for 1 h, then concentrated in vacuo. The residue obtained was dissolved in DCM, washed with NaHCO3 (aq.), and then the organic layer was concentrated and purified by prep-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; 25% acetonitrile/75% water (doped with 0.1% TFA, v/v) to 42% acetonitrile/58% water (doped with 0.1% TFA, v/v) over 9 min) to give 2-(6-fluoro-1-(3-(methylsulfonyl)propyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (10 mg, 50%) as a white solid. 1H NMR (300 MHz, DMSO): δ 12.81 (s, 1H), 9.10 (s, 1H), 8.63-8.58 (m, 1H), 8.37 (s, 1H), 7.90 (s, 1H), 7.71 (d, 1H, J=8.1 Hz), 7.16 (t, 1H, J=9.2 Hz), 5.08 (t, 1H, J=5.5 Hz), 4.62 (t, 2H, J=6.6 Hz), 3.60 (d, 2H, J=5.4 Hz), 3.18 (t, 2H, J=6.4 Hz), 2.96 (s, 3H), 2.32 (t, 2H, J=7.6 Hz), 1.43 (s, 6H). LC/MS: 489.2 [M+H]+, 487.0 [M−H]−.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue obtained
  3. washwashed with NaHCO3 (aq.)
  4. concentrationthe organic layer was concentrated
  5. custompurified by prep-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; 25% acetonitrile/75% water (doped with 0.1% TFA, v/v) to 42% acetonitrile/58% water (doped with 0.1% TFA, v/v) over 9 min)

Sources & evidence

ORD record
ord-d0686f4e6f8b4fe193fcb5d7a6eba9b3
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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