Sodium Bicarbonate → HCID 86659281, compound

HRID 2362651Notes

Reaction equation

HRID 2362651 reaction equation
[Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([O:31][CH2:32][O:33][CH3:34])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9](I)[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1.[F:35][C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][C:41]=1[CH:42]=[O:43].C(=O)(O)[O-].[Na+]>CN(C)C=O.O.[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([O:31][CH2:32][O:33][CH3:34])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9]([C:38]3[CH:39]=[CH:40][C:41]([CH:42]=[O:43])=[C:36]([F:35])[CH:37]=3)[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 27786543-Fluoro-4-formylphenylboronic acidHCID 67003444HCID 67003444, compound

Product 1

HCID 86659281HCID 86659281, compound

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 5-(5-chloro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-2-(1-(methoxymethoxy)cyclobutyl)thiazole (580 mg, 0.921 mmol) (Example 1F), 3-fluoro-4-formylphenylboronic acid (309 mg, 1.842 mmol), and bis(triphenylphosphine)palladium dichloride (32.3 mg, 0.046 mmol) in N,N-dimethylformamide (12 ml) was added saturated aqueous sodium bicarbonate solution (12 mL). The mixture was heated to 65° C. under an atmosphere of nitrogen for about 90 minutes. The reaction mixture was cooled to room temperature, and diluted with water (about 50 mL) and saturated brine solution (about 25 mL). The aqueous layer was extracted with ethyl acetate (3×30 mL), and the combined organics were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 0 to 30% ethyl acetate in hexane, to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.30 (s, 1H), 8.63-8.60 (m, 1H), 8.23 (s, 1H), 7.95 (t, 1H), 7.81-7.72 (m, 3H), 7.65 (dd, 1H), 7.40 (d, 2H), 7.14 (d, 1H), 4.76 (s, 2H), 2.71-2.54 (m, 2H), 2.35 (s, 3H), 2.01-1.88 (m, 3H). MS APCI(+) m/z 626.42 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe aqueous layer was extracted with ethyl acetate (3×30 mL)
  3. washthe combined organics were washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel
  8. washeluting with a gradient of 0 to 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-bb268e265a6e46a591896195fb735cfa
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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