Hydrochloric Acid → HCID 86677979, compound

HRID 246418Notes

Reaction equation

HRID 246418 reaction equation
[O:1]1CCCO[CH:2]1[CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH:19]([F:21])[F:20])=[CH:15][CH:16]=2)[C:11]([C:22]2[N:23]=[C:24]3[C:30]([C:31]([NH:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[CH:29][N:28]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[C:25]3=[N:26][CH:27]=2)=[N:10]1.Cl.C(=O)([O-])O.[Na+]>C1COCC1>[C:34]([NH:33][C:31]([C:30]1[C:24]2[C:25](=[N:26][CH:27]=[C:22]([C:11]3[C:12]4[C:17](=[CH:16][CH:15]=[C:14]([O:18][CH:19]([F:21])[F:20])[CH:13]=4)[N:9]([CH2:8][CH2:7][CH:2]=[O:1])[N:10]=3)[N:23]=2)[N:28]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[CH:29]=1)=[O:32])([CH3:36])([CH3:35])[CH3:37]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 516892Sodium BicarbonateHCID 71279842HCID 71279842, compound

Product 1

HCID 86677979HCID 86677979, compoundYield 28.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

2-(1-(2-(1,3-Dioxan-2-yl)ethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (130 mg, 202 μmol) was dissolved in THF (3 mL), and HCl 3N (672 μL, 2.02 mmol0.00) was added. After stirring the mixture at 25° C. overnight, TLC and LCMS showed about 10% conversion. Added 0.5 mL of concentrated HCl and reaction heated to 50° C. for 48 h more. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with dichloromethane (5×30 mL). The obtained organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated, and the obtained residue was purified by silica gel chromatography (n-hexane-ethyl acetate 0 to 100% over 30 min to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-oxopropyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (34 mg, 58.0 μmol, 28.7%). MS (M+H)+=587; 1H NMR (CDCl3) δ: 9.97 (s, 1H), 9.20 (s, 1H), 8.42 (s, 1H), 8.30 (d, J=2.3 Hz, 1H), 8.08 (s, 1H), 7.63 (d, J=9.1 Hz, 1H), 7.39 (dd, J=9.1, 2.3 Hz, 1H), 6.54 (t, J=74.4 Hz, 1H), 5.75 (s, 2H), 5.34 (s, 1H), 4.82 (t, J=6.2 Hz, 2H), 3.55-3.65 (m, 2H), 3.33 (t, J=6.4 Hz, 2H), 1.64 (s, 9H), 0.90-1.05 (m, 2H), 0.05-0.07 (m, 1H), 0.00 (s, 9H). Unreacted starting material (31 mg, 24%) as also obtained.

Workup

  1. additionAdded
  2. temperatureheated to 50° C. for 48 h more
  3. extractionthe mixture was extracted with dichloromethane (5×30 mL)
  4. dry with materialThe obtained organic layer was dried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated
  6. customthe obtained residue was purified by silica gel chromatography (n-hexane-ethyl acetate 0 to 100% over 30 min

Sources & evidence

ORD record
ord-601ce563933045db8e7677182e790bf1
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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