Sodium Bicarbonate → 3-amino-6-[4-chloro-3-(5-fluoro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrazine-2-carboxylic acid dimethylamide

HRID 1693727Notes

Reaction equation

HRID 1693727 reaction equation
[Cl:1][C:2]1[C:7](B(O)O)=[CH:6][N:5]=[C:4]2[N:11]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH:12]=[C:13]([C:14]3[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=3[O:21][CH3:22])[C:3]=12.[CH3:31][N:32]([CH3:43])[C:33]([C:35]1[C:40]([NH2:41])=[N:39][CH:38]=[C:37](I)[N:36]=1)=[O:34].C(=O)(O)[O-].[Na+]>C(#N)C.C1(C)C=CC=CC=1.ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:31][N:32]([CH3:43])[C:33]([C:35]1[C:40]([NH2:41])=[N:39][CH:38]=[C:37]([C:7]2[C:2]([Cl:1])=[C:3]3[C:13]([C:14]4[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=4[O:21][CH3:22])=[CH:12][N:11]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:4]3=[N:5][CH:6]=2)[N:36]=1)=[O:34]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 575376124-chloro-3-(5-fluoro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine-5-boronic acidHCID 575376613-Amino-6-iodo-pyrazine-2-carboxylic acid dimethylamide

Product 1

HCID 575376463-amino-6-[4-chloro-3-(5-fluoro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrazine-2-carboxylic acid dimethylamideYield 47.3%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

42 mg (93 μmol) of 4-chloro-3-(5-fluoro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine-5-boronic acid, 5 mg (6 μmol) of (1,1′-bis(diphenylphosphino)ferrocene palladium(II)-dichloride dichloromethane adduct and 41 mg (0.14 mmol) of 3-amino-6-iodo-pyrazine-2-carboxylic acid dimethylamide were dissolved in a mixture of 1 mL of acetonitrile and 1 mL of toluene. 2 mL of a saturated aqueous solution of sodium bicarbonate was added and the resulting mixture heated in closed vial to 110° C. for 20 h. The aqueous layer was removed and the organic phase evaporated. The residue was purified by flash chromatography on silica gel using a gradient of 10% v/v of methanol in ethyl acetate and hexanes to afford 25 mg (44 μmol, 47%) of 3-amino-6-[4-chloro-3-(5-fluoro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyrazine-2-carboxylic acid dimethylamide.

Workup

  1. customThe aqueous layer was removed
  2. customthe organic phase evaporated
  3. customThe residue was purified by flash chromatography on silica gel using a gradient of 10% v/v of methanol in ethyl acetate and hexanes

Sources & evidence

ORD record
ord-3f5e5933a72c4325a6ed8017018d60e3
Source dataset
uspto-grants-2012_04
Patent number
US08158647B2

Reaction notes

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