Water → 5-[4-chloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-nicotinic acid ethyl ester

HRID 1693706Notes

Reaction equation

HRID 1693706 reaction equation
Br[C:2]1[C:3]([Cl:19])=[C:4]2[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1.[CH2:20]([O:22][C:23]([C:25]1[CH:26]=[N:27][CH:28]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:30]=1)=[O:24])[CH3:21].ClCCl.O>C(#N)C.C1(C)C=CC=CC=1.C(=O)(O)[O-].[Na+]>[CH2:20]([O:22][C:23](=[O:24])[C:25]1[CH:30]=[C:29]([C:2]2[C:3]([Cl:19])=[C:4]3[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]3=[N:6][CH:7]=2)[CH:28]=[N:27][CH:26]=1)[CH3:21]

Participants

8

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 3816953Ethyl 5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carboxylateHCID 575376665-Bromo-4-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo(2,3-b)pyridine

Product 1

HCID 575375885-[4-chloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-nicotinic acid ethyl esterYield 56.4%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
110 °C

Procedure

1.59 g (4.40 mmol) of 5-bromo-4-chloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine, 1.482 g (5.35 mmol) of 3-(ethoxycarbonyl)pyridine-5-boronic acid pinacol ester and 181 mg (0.22 mmol) of (1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct were dissolved in a mixture of 7 mL of acetonitrile, 7 mL of toluene and 8 mL of a saturated aqueous solution of sodium bicarbonate. The resulting mixture was heated to 110° C. in a closed vial for 15 h. The resulting mixture was distributed between dichloromethane and water. The aqueous phase was separated and extracted three times with dichloromethane and the once with ethyl acetate. The ethyl acetate phase was washed with brine and combined with the other organic phases, dried over sodium sulfate and evaporated. The resulting crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes to afford 1.0703 g (2.48 mmol, 56%) of 5-[4-chloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-nicotinic acid ethyl ester as a pale yellow oil. 1H-NMR [500 MHz, d6-DMSO] δ: 9.15 (d, 1H), 8.97 (d, 1H), 8.41 (m, 1H), 8.40 (m, 1H), 7.89 (d, 1H), 5.69 (s, 2H), 4.38 (q, 2H), 3.55 (t, 2H), 1.35 (t, 3H), 0.84 (t, 2H), −0.08 (s, 9H); MS [MH+] m/z: 432+434.

Workup

  1. customThe aqueous phase was separated
  2. extractionextracted three times with dichloromethane
  3. washThe ethyl acetate phase was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customThe resulting crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-0e0f4ba479414ce988f2b50623931f96
Source dataset
uspto-grants-2012_04
Patent number
US08158647B2

Reaction notes

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