Bicarbonate Ion → HCID 67003555, compound

HRID 2362643Notes

Reaction equation

HRID 2362643 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.[N:41]1([CH2:46][CH2:47][N:48]2[CH:52]=[C:51](B3OC(C)(C)C(C)(C)O3)[CH:50]=[N:49]2)[CH2:45][CH2:44][CH2:43][CH2:42]1.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:51]3[CH:50]=[N:49][N:48]([CH2:47][CH2:46][N:41]4[CH2:45][CH2:44][CH2:43][CH2:42]4)[CH:52]=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 588858611-(2-(pyrrolidin-1-yl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 67003856HCID 67003856, compound

Product 1

HCID 67003555HCID 67003555, 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) (300 mg, 0.424 mmol) and 1-(2-(pyrrolidin-1-yl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (Example 20A) (173 mg, 0.593 mmol) in N,N-dimethylformamide (3.97 mL) was added saturated aqueous bicarbonate solution (1.32 mL) followed by bis(triphenylphosphine)palladium dichloride (20.8 mg, 0.030 mmol). The mixture was heated to 70° C. for 4 hours, cooled to room temperature, and 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 10% methanol in dichloromethane, to afford the title compound. MS ESI(+) m/z 745.1 [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. customquenched by the addition of water and ethyl acetate
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with additional ethyl acetate
  5. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel
  9. washeluting with a gradient of 0 to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-c81ed900bd694a5ba8a0e65b43c6f203
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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