Acetonitrile → (1R,2S,6R)-2-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-6-methoxycyclohexanol

HRID 74990Notes

Reaction equation

HRID 74990 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.C(#N)C.Cl[C:34]1[N:39]=[C:38]([NH:40][C@H:41]2[CH2:46][CH2:45][CH2:44][C@@H:43]([O:47][CH3:48])[C@@H:42]2[OH:49])[C:37]([F:50])=[CH:36][N:35]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:34]3[N:39]=[C:38]([NH:40][C@H:41]4[CH2:46][CH2:45][CH2:44][C@@H:43]([O:47][CH3:48])[C@@H:42]4[OH:49])[C:37]([F:50])=[CH:36][N:35]=3)=[CH:9][N:8]([S:20]([C:23]3[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=3)(=[O:21])=[O:22])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 575977475-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 86667434HCID 86667434, compound2×

Product 1

HCID 68007375(1R,2S,6R)-2-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-6-methoxycyclohexanol

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

In a microwave tube was placed 5-chloro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (0.10 g, 0.23 mmol). To this was added acetonitrile (0.61 mL) and the solution was deoxygenated with nitrogen. To the reaction was added (1R,2S,6R)-2-(2-chloro-5-fluoropyrimidin-4-ylamino)-6-methoxy-cyclohexanol, 51j, (0.04 g, 0.14 mmol) and palladium catalyst (24 mg), and then aqueous sodium carbonate (0.21 mL of 2 M solution, 0.41 mmol). The reaction was sealed and heated to 120° C. in the microwave reactor for 15 min. The reaction was diluted with ethyl acetate (40 mL), filtered thru florisil, and concentrated in vacuo to give crude as a green solid. This was purified by silica gel chromatography (20-75% EtOAc/hexanes gradient). Used resulting product directly in the next step.

Workup

  1. customIn a microwave tube was placed
  2. customthe solution was deoxygenated with nitrogen
  3. customThe reaction was sealed
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give crude as a green solid
  7. customThis was purified by silica gel chromatography (20-75% EtOAc/hexanes gradient)
  8. customUsed resulting product directly in the next step

Sources & evidence

ORD record
ord-7a32c1ab536a4872b39307b9fafd2d73
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

Loading…