HCID 71280109, compound → HCID 71279865, compound

HRID 246610Notes

Reaction equation

HRID 246610 reaction equation
[Si]([O:8][CH2:9][CH2:10][C:11]([NH:14][C:15]([C:17]1[C:25]2[C:20](=[N:21][CH:22]=[C:23]([C:26]3[C:34]4[C:29](=[CH:30][C:31]([F:35])=[CH:32][CH:33]=4)[N:28]([CH3:36])[N:27]=3)[N:24]=2)[NH:19][CH:18]=1)=[O:16])([CH3:13])[CH3:12])(C(C)(C)C)(C)C>Cl.O1CCOCC1>[F:35][C:31]1[CH:30]=[C:29]2[C:34]([C:26]([C:23]3[N:24]=[C:25]4[C:17]([C:15]([NH:14][C:11]([CH3:13])([CH2:10][CH2:9][OH:8])[CH3:12])=[O:16])=[CH:18][NH:19][C:20]4=[N:21][CH:22]=3)=[N:27][N:28]2[CH3:36])=[CH:33][CH:32]=1

Participants

4

Reactant 1

HCID 71280109HCID 71280109, compound

Product 1

HCID 71279865HCID 71279865, compoundYield 27.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

N-(4-(tert-butyldimethylsilyloxy)-2-methylbutan-2-yl)-2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (70 mg, 0.140 mmol) was dissolved in 30 mL of a saturated solution of HCl (g) in dioxane and the solution was stirred at room temperature for one hour. The solvent was evaporated at 40° C. 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 42% acetonitrile/58% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(4-hydroxy-2-methylbutan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (15 mg, 27.6%) as a yellow solid. MS: (M+H)+=397; 1H NMR (300 MHz, DMSO): δ 12.84 (s, 1H), 9.10 (s, 1H), 8.55-8.50 (m, 1H), 8.40 (s, 1H), 7.89 (s, 1H), 7.73-7.69 (m, 1H), 7.22-7.16 (m, 1H), 7.42 (t, 2H, J=4.6 Hz), 4.17 (s, 3H), 3.61-3.55 (m, 2H), 2.13-2.09 (m, 2H), 1.25 (s, 6H).

Workup

  1. customThe solvent was evaporated at 40° C. 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 42% acetonitrile/58% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

Sources & evidence

ORD record
ord-723505bdfcc44473850f0b61e77e50f9
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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