Ammonia → {(3aR,4R,6R,6aS)-2,2-dimethyl-6-[6-(phenylethynyl)-9H-purin-9-yl]tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methanol

HRID 552727Notes

Reaction equation

HRID 552727 reaction equation
C([O:4][CH2:5][C@@H:6]1[C@@H:13]2[C@@H:9]([O:10][C:11]([CH3:15])([CH3:14])[O:12]2)[C@H:8]([N:16]2[CH:24]=[N:23][C:22]3[C:17]2=[N:18][CH:19]=[N:20][C:21]=3I)[CH2:7]1)(=O)C.CCN(C(C)C)C(C)C.[C:35]1([C:41]#[CH:42])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.N>CN(C=O)C.C(Cl)Cl.CO.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.[Cu]I>[CH3:14][C:11]1([CH3:15])[O:10][C@H:9]2[C@H:8]([N:16]3[CH:24]=[N:23][C:22]4[C:17]3=[N:18][CH:19]=[N:20][C:21]=4[C:42]#[C:41][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH2:7][C@H:6]([CH2:5][OH:4])[C@H:13]2[O:12]1

Participants

10

Reactant 4

HCID 222AmmoniaHCID 10821PhenylacetyleneHCID 81531DiisopropylethylamineHCID 86607317[(3aR,4R,6R,6aS)-6-(6-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methyl acetate

Product 1

HCID 67165047{(3aR,4R,6R,6aS)-2,2-dimethyl-6-[6-(phenylethynyl)-9H-purin-9-yl]tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methanolYield 63%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of [(3aR,4R,6R,6aS)-6-(6-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methyl acetate (140.0 mg, 0.31 mmol), Pd(PPh3)2Cl2 (25 mg, 0.036 mmol), DIPEA (140 μL, 0.80 mmol), CuI (20 mg, 0.1 mmol) and phenylacetylene (170 μL, 1.5 mmol) in DMF (5.0 mL) under an atmosphere of nitrogen was stirred at room temperature for 20 minutes. The reaction was concentrated and the residue taken up in DCM (50 mL). This was washed with saturated aq EDTA.Na2 (2×10 mL) then water (10 mL). The organics were concentrated to provide a black gum. This crude product was dissolved in DCM (5 mL) and 7.0 M of ammonia in methanol (5.0 mL) was added. This was stirred at room temperature for 2 hours. The reaction was concentrated and the residue was purified by flash chromatography (0 to 100% EtOAc/DCM) to provide the title compound (75 mg, 63%).

Workup

  1. concentrationThe reaction was concentrated
  2. washThis was washed with saturated aq EDTA
  3. concentrationThe organics were concentrated
  4. customto provide a black gum
  5. concentrationThe reaction was concentrated
  6. customthe residue was purified by flash chromatography (0 to 100% EtOAc/DCM)

Sources & evidence

ORD record
ord-03b6400e4e574040b240681c391f6208
Source dataset
uspto-grants-2011_05
Patent number
US07951810B2

Reaction notes

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