Sodium Carbonate → tert-butyl 4-(5-methoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 2378978Notes

Reaction equation

HRID 2378978 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH:9]=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+].FC(F)(F)S(O[C:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH:31]=1)(=O)=O>O.O1CCOCC1>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH:9]=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[C:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH:31]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 59006378B-(5-methoxy-1-methyl-1h-pyrrolo[3,2-b]pyridin-6-yl)-boronic acid

Product 1

HCID 59006345tert-butyl 4-(5-methoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To 5-methoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-ylboronic acid (398 mg, 1.932 mmol) was added sodium carbonate (410 mg, 3.86 mmol), lithium chloride (164 mg, 3.86 mmol), tert-butyl 4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (640 mg, 1.932 mmol) and deairared 1,4-Dioxane (15 mL) at rt temperature, followed by tetrakis (triphenylphosphine)pladdinum (0) (112 mg, 0.097 mol), and H2O (1 mL). The resulting light brown mixture was stirred at 80° C. for 2 hr. After cooling down to rt, the mixture was partitioned between H2O/EtOAc (30 mL/50 mL), and separated. The organic layer was washed with brine (10 mL), dried (Na2SO4), concentrated on rotary vacuo, purified on Biotage Flash Collector eluting with 30˜80% EtOAc/Hexanes (1200 mL) to afford the expected product, tert-butyl 4-(5-methoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate (207 mg, 32%). 1H-NMR (400 MHz, MeOD) δ ppm 1.44-1.51 (m, 9 H) 2.51 (d, J=1.51 Hz, 2 H) 3.59 (s, 2 H) 3.78 (s, 3 H) 3.93 (s, 3 H) 4.04 (s, 2 H) 4.86 (s, 1 H) 5.82 (s, 1 H) 6.39 (d, J=2.52 Hz, 1 H) 7.27 (d, J=3.27 Hz, 1 H) 7.58 (s, 1 H); Mass spec 344.18 (MH+) Calc for C19H25N3O3 343.19.

Workup

  1. temperatureAfter cooling down to rt
  2. customthe mixture was partitioned between H2O/EtOAc (30 mL/50 mL)
  3. customseparated
  4. washThe organic layer was washed with brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated on rotary vacuo
  7. custompurified on Biotage Flash Collector
  8. washeluting with 30˜80% EtOAc/Hexanes (1200 mL)

Sources & evidence

ORD record
ord-30e7d941217647e09bd33aa851beb2e5
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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