Bicarbonate Ion → HCID 67003360, compound

HRID 2362633Notes

Reaction equation

HRID 2362633 reaction equation
[Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([O:31][CH2:32][C:33]4[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=4)[CH2:30][O: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:49]2[CH:61]=[CH:60][C:52]([CH2:53][N:54]3[CH2:59][CH2:58][O:57][CH2:56][CH2:55]3)=[CH:51][CH:50]=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][C:33]4[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=4)[CH2:30][O:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9]([C:49]3[CH:61]=[CH:60][C:52]([CH2:53][N:54]4[CH2:59][CH2:58][O:57][CH2:56][CH2:55]4)=[CH:51][CH:50]=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 27955024-((Morpholino)methyl)phenylboronic acid pinacol esterHCID 67003856HCID 67003856, compound

Product 1

HCID 67003360HCID 67003360, 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-(3-(4-methoxybenzyloxy)oxetan-3-yl)thiazole (Example 11G) (200 mg, 0.282 mmol) and 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)morpholine (120 mg, 0.395 mmol) in N,N-dimethylformamide (2.65 mL) was added saturated aqueous bicarbonate solution (0.883 mL) followed by bis(triphenylphosphine)palladium dichloride (13.88 mg, 0.020 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 residue was purified by flash chromatography on silica gel, eluting with a gradient of 0 to 30% ethyl acetate in hexane, to afford the title compound. MS ESI(+) m/z 757.2 [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 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-f79ad057e24345228d187ad90dfac5ba
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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