Cesium carbonate → ((3aR,4R,6R,6aS)-6-(6-Methoxy-2-(methylthio)-5-(thiazolo[4,5-c]pyridin-2-yl)pyrimidin-4-ylamino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

HRID 1507482Notes

Reaction equation

HRID 1507482 reaction equation
I[C:2]1[C:3]([NH:12][C@H:13]2[C@@H:17]3[O:18][C:19]([CH3:22])([CH3:21])[O:20][C@@H:16]3[C@@H:15]([CH2:23][OH:24])[CH2:14]2)=[N:4][C:5]([S:10][CH3:11])=[N:6][C:7]=1[O:8][CH3:9].[S:25]1[C:33]2[CH:32]=[CH:31][N:30]=[CH:29][C:28]=2[N:27]=[CH:26]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][O:8][C:7]1[N:6]=[C:5]([S:10][CH3:11])[N:4]=[C:3]([NH:12][C@H:13]2[C@@H:17]3[O:18][C:19]([CH3:22])([CH3:21])[O:20][C@@H:16]3[C@@H:15]([CH2:23][OH:24])[CH2:14]2)[C:2]=1[C:26]1[S:25][C:33]2[CH:32]=[CH:31][N:30]=[CH:29][C:28]=2[N:27]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 585837Thiazolo[4,5-c]pyridineHCID 117677839((3aR,4R,6R,6aS)-6-(5-Iodo-6-methoxy-2-(methylthio)pyrimidin-4-ylamino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

Product 1

HCID 117677843((3aR,4R,6R,6aS)-6-(6-Methoxy-2-(methylthio)-5-(thiazolo[4,5-c]pyridin-2-yl)pyrimidin-4-ylamino)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Compound 6 (467 mg, 1.00 mmol), thiazolo[4,5-c]pyridine (272 mg, 2.00 mmol), CuI (67.0 mg, 0.350 mmol), cesium carbonate (1.95 mg, 6.00 mmol) and Pd(Ph3P)4 (231 mg, 0.200 mmol) were combined and suspended in DMF (10 mL). The reaction was degassed and heated to 100° C. for a 1 h. The reaction mixture was cooled to room temperature, extracted twice with ethyl acetate. The combined organics were washed with water, brine, dried (MgSO4), filtered and concentrated. The residue was then purified by column chromatrography on silica gel (MeOH/DCM) to give the title compound. LCMS 1.90 min, 476 (M+H)

Workup

  1. customThe reaction was degassed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted twice with ethyl acetate
  4. washThe combined organics were washed with water, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was then purified by column chromatrography on silica gel (MeOH/DCM)

Sources & evidence

ORD record
ord-40bfeff09366453d8513e33d2ed3990b
Source dataset
uspto-grants-2015_12
Patent number
US09221809B2

Reaction notes

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