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

HRID 2378974Notes

Reaction equation

HRID 2378974 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH:9]=[CH:10][N:11]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[C:6]2=[CH:5][C:4]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+].FC(F)(F)S(O[C:39]1[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH:40]=1)(=O)=O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.O1CCOCC1>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH:9]=[CH:10][N:11]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[C:6]2=[CH:5][C:4]=1[C:39]1[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH:40]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 590063505-methoxy-1-(triisopropylsilyl)-1H-pyrrolo[3,2-b]pyridin-6-ylboronic acid

Product 1

HCID 59006352tert-butyl 4-(5-methoxy-1-(triisopropylsilyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 80%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To 5-methoxy-1-(triisopropylsilyl)-1H-pyrrolo[3,2-b]pyridin-6-ylboronic acid (900 mg, 2.58 mmol) was added sodium carbonate (548 mg, 5.17 mmol), lithium chloride (219 mg, 5.17 mmol), tert-butyl 4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (856 mg, 2.58 mmol) and deairared 1,4-dioxane (15 mL) at rt temperature, followed by tetrakis(triphenylphosphine)palladium(0) (149 mg, 0.1297 mol), and H2O (1 mL). The resulting light brown mixture was stirred at 80° C. for 2 hr, and the conversion was completed as determined by LC/MS. After cooling down to rt, the mixture was partitioned between H2O/EtOAc (50 mL/100 mL). After separation, the organic phase was washed with brine, dried (Na2SO4), concentrated on rotary vacuo, and purified on Biotage Flash Collector eluting with 30-80% EtOAc/Hexanes (1200 mL) to afford the expected product, tert-butyl 4-(5-methoxy-1-(triisopropylsilyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate (998 mg, 80%) as a white solid. 1H-NMR (400 MHz, MeOD) δ ppm 1.12 (s, 18 H) 1.49 (s, 9 H) 2.52 (s, 2 H) 3.47 (s, 3 H) 3.62 (s, 2 H) 4.00 (s, 3 H) 4.09 (s, 2 H) 5.78 (s, 1 H) 6.65 (s, 1 H) 7.33(s, 1 H) 7.51 (s, 1 H). Mass spec 486.28 (MH+) Calc for C27H43N3O3Si 485.31.

Workup

  1. temperatureAfter cooling down to rt
  2. customthe mixture was partitioned between H2O/EtOAc (50 mL/100 mL)
  3. customAfter separation
  4. washthe organic phase was washed with brine
  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-0f7c70b0939a4e9692ddce41cbb67eaf
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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