Bicarbonate Ion → HCID 67003839, compound

HRID 2362621Notes

Reaction equation

HRID 2362621 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.CC1(C)C(C)(C)OB([C:43]2[CH:44]=[N:45][N:46]([CH2:48][CH2:49][N:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)[CH:47]=2)O1.C(=O)(O)[O-]>CN(C)C=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:43]3[CH:44]=[N:45][N:46]([CH2:48][CH2:49][N:50]4[CH2:55][CH2:54][O:53][CH2:52][CH2:51]4)[CH:47]=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

6

Reactant 3

HCID 769Bicarbonate IonHCID 177499241-(2-Morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 67003444HCID 67003444, compound

Product 1

HCID 67003839HCID 67003839, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred ambient solution of 5-(5-chloro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-2-(1-(methoxymethoxy)cyclobutyl)thiazole (Example 1F) (200 mg, 0.318 mmol) and 4-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)ethyl)morpholine (127 mg, 0.413 mmol) in N,N-dimethylformamide (0.79 mL) was added saturated aqueous bicarbonate solution (0.79 mL) followed by bis(triphenylphosphine)palladium dichloride (15.60 mg, 0.022 mmol). The mixture was heated to 70° C. for 4 hours and was then quenched by the addition of water and ethyl acetate. The layers were separated, and the aqueous layer was extracted with additional ethyl acetate. The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel, eluting with a gradient of 20% ethyl acetate in hexane to 100% ethyl acetate with 3% methanol, to afford the title compound. MS ESI(+) m/z 683.52 [M+H]+.

Workup

  1. customwas then quenched by the addition of water and ethyl acetate
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with additional ethyl acetate
  4. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by flash chromatography on silica gel
  8. washeluting with a gradient of 20% ethyl acetate in hexane to 100% ethyl acetate with 3% methanol

Sources & evidence

ORD record
ord-76f405e0ea664be7a27f22b3133afd0e
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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