Hydrochloric Acid → HCID 86677979, compound

HRID 246421Notes

Reaction equation

HRID 246421 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+]>CC(C)=O>[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 AcidHCID 516892Sodium BicarbonateHCID 71279842HCID 71279842, compound

Product 1

HCID 86677979HCID 86677979, compoundYield 29.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
50 °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 (100 mg, 155 μmol) was dissolved in acetone (3 mL), and HCl 3N (1.2 g, 1 mL, 3.00 mmol9.3) was added. Heated to 50° C. with stirring and continued for 5 days. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with dichloromethane (5×30 mL). The combined organic layers were 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 20 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 (27 mg, 46.0 μmol, 29.7%) and a small amount of the SEM group de-protection product 2-(1-(2-(1,3-dioxan-2-yl)ethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (5 mg, 9.72 μmol, 6.27%) as light yellow needles. MS (M+H)+=515; 1H NMR (DMSO-d6) δ: 12.80 (br. s., 1H), 9.08 (s, 1H), 8.37 (s, 1H), 8.20 (d, J=2.3 Hz, 1H), 7.87 (s, 1H), 7.81 (d, J=9.1 Hz, 1H), 7.39 (dd, J=9.1, 2.3 Hz, 1H), 7.19 (t, J=74.4 Hz, 1H), 4.45-4.72 (m, 3H), 3.99 (dd, J=11.3, 4.5 Hz, 2H), 3.55-3.75 (m, 2H), 2.07-2.22 (m, 2H), 1.79-1.97 (m, 1H), 1.49 (s, 9H), 1.38 (s, 9H), 134 (m, 1H). Unreacted starting material (34 mg, 34%) was also obtained.

Workup

  1. extractionthe mixture was extracted with dichloromethane (5×30 mL)
  2. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated
  4. customthe obtained residue was purified by silica gel chromatography (n-hexane-ethyl acetate 0 to 100% over 20 min)

Sources & evidence

ORD record
ord-5933c439a0b046afa6737167a7b80e3d
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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