Water → HCID 86692836, compound

HRID 928247Notes

Reaction equation

HRID 928247 reaction equation
[CH3:1][C:2]1([CH3:31])[O:6][C@H:5]2[C@H:7]([NH:12][C:13]3[N:18]4[N:19]=[C:20](B5OC(C)(C)C(C)(C)O5)[CH:21]=[C:17]4[N:16]=[CH:15][CH:14]=3)[CH2:8][C@H:9]([CH2:10][OH:11])[C@H:4]2[O:3]1.[Cl:32][C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36](I)=[CH:35][CH:34]=1.ClCCl.C(=O)([O-])[O-].[Cs+].[Cs+].O>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:32][C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]([C:20]2[CH:21]=[C:17]3[N:16]=[CH:15][CH:14]=[C:13]([NH:12][C@H:7]4[C@@H:5]5[O:6][C:2]([CH3:1])([CH3:31])[O:3][C@@H:4]5[C@@H:9]([CH2:10][OH:11])[CH2:8]4)[N:18]3[N:19]=2)=[CH:35][CH:34]=1

Participants

8

Reactant 5

HCID 962WaterHCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 2307691-chloro-4-iodonaphthaleneHCID 86692837HCID 86692837, compound

Product 1

HCID 86692836HCID 86692836, compoundYield 167%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A microwave vial is charged with ((3aR,4R,6R,6aS)-2,2-dimethyl-6-{[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl]amino}tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol (0.25 g, 0.58 mmol), 1-chloro-4-iodo-naphthalene (0.38 g, 1.30 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (29 mg, 0.036 mmol), cesium carbonate (0.70 g, 2.2 mmol) 1,4-dioxane (4.0 mL, 50 mmol) and water (0.60 mL, 30 mmol). The reaction mixture is heated in the microwave at 110° C. for 30 minutes and then cooled to room temperature. The reaction mixture is diluted with ethyl acetate and was washed successively with water, saturated sodium bicarbonate solution and brine. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo. The crude material is purified by column chromatography (0-80% ethyl actate/hexanes) to provide (s.e.)-[(3aR,4R,6R,6aS)-6-{[2-(4-chloro-1-naphthyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanol (0.450 g, yield 167%). LCMS: (AA) M+1 465.

Workup

  1. temperaturecooled to room temperature
  2. washwas washed successively with water, saturated sodium bicarbonate solution and brine
  3. dry with materialThe organic layer is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material is purified by column chromatography (0-80% ethyl actate/hexanes)

Sources & evidence

ORD record
ord-98a05440e2164719aa3931da61cbe50b
Source dataset
uspto-grants-2016_03
Patent number
US09290500B2

Reaction notes

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