Hydrochloric Acid → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(3-methylpyrrolidin-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide hydrochloride

HRID 246623Notes

Reaction equation

HRID 246623 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:23][C:24]5([CH3:37])C[CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]5)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[ClH:38]>O1CCOCC1>[ClH:38].[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:23][C:24]5([CH3:37])[CH2:25][CH2:26][NH:27][CH2:28]5)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 71280124HCID 71280124, compound

Product 1

HCID 712796332-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(3-methylpyrrolidin-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide hydrochlorideYield 36.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 4-(2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)-4-methylpiperidine-1-carboxylate (103 mg, 0.20 mmol) was dissolved in 20 mL of a saturated solution of HCl (g) in dioxane and the mixture was stirred at room temperature for 2 hours. 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: 20% acetonitrile/80% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 40% acetonitrile/60% 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-(3-methylpyrrolidin-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide hydrochloride (30 mg, 36.5%) as a pale yellow solid. MS: (M+H)+=408; 1H NMR (300 MHz, DMSO): δ 9.16 (s, 1H), 8.57-8.41 (m, 4H), 7.92 (s, 1H), 7.75 (d, 1H, J=10.5 Hz), 7.32-7.26 (m, 1H), 6.98-6.93 (m, 1H), 5.75 (d, 2H, J=6.9 Hz), 4.19 (s, 3H), 3.16 (brs, 5H), 1.96 (brs, 3H), 1.61 (s, 3H).

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. wait20% acetonitrile/80% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 40% acetonitrile/60% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

Sources & evidence

ORD record
ord-1d336c1180994ccaade9e095e1710889
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…