Diisopropylethylamine → [(3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-{[2-(trifluoromethyl)phenyl]ethynyl}-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl sulfamate

HRID 552746Notes

Reaction equation

HRID 552746 reaction equation
[S:1](=[O:26])(=[O:25])([O:3][CH2:4][C@@H:5]1[C@@H:12]2[C@@H:8]([O:9][C:10]([CH3:14])([CH3:13])[O:11]2)[C@H:7]([N:15]2[CH:23]=[N:22][C:21]3[C:16]2=[N:17][CH:18]=[N:19][C:20]=3I)[O:6]1)[NH2:2].CCN(C(C)C)C(C)C.[C:36]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[C:44]([F:47])([F:46])[F:45])#[CH:37]>CN(C=O)C.C(Cl)Cl.[Cu]I.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>[S:1](=[O:26])(=[O:25])([O:3][CH2:4][C@@H:5]1[C@@H:12]2[C@@H:8]([O:9][C:10]([CH3:14])([CH3:13])[O:11]2)[C@H:7]([N:15]2[CH:23]=[N:22][C:21]3[C:16]2=[N:17][CH:18]=[N:19][C:20]=3[C:37]#[C:36][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[C:44]([F:45])([F:46])[F:47])[O:6]1)[NH2:2]

Participants

8

Reactant 3

HCID 81531DiisopropylethylamineHCID 41008561-Ethynyl-2-(trifluoromethyl)benzeneHCID 86607325[(3aR,4R,6R,6aR)-6-(6-iodo-9H-purin-9-yl)-2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl sulfamate

Product 1

HCID 86607327[(3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-{[2-(trifluoromethyl)phenyl]ethynyl}-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl sulfamateYield 85.3%

Reagents, catalysts & solvents 4

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

Procedure

To a solution of [(3aR,4R,6R,6aR)-6-(6-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl sulfamate (0.200 g, 0.402 mmol) in DMF (7 mL) was added DIPEA (0.176 mL, 1.01 mmol), 1-ethynyl-2-trifluoromethyl-benzene (0.224 mL, 1.61 mmol), CuI (0.0191 g, 0.101 mmol), and Pd(PPh3)2Cl2 (0.0282 g, 0.0402 mmol). The mixture was stirred at r.t. for 50 min, diluted with DCM (25 mL) and washed with saturated aq EDTA.Na2 (3×25 mL). The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography (15 to 50% EtOAc/DCM) to isolate the title compound (0.185 g, 85%).

Workup

  1. washwashed with saturated aq EDTA
  2. washThe combined organics were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography (15 to 50% EtOAc/DCM)

Sources & evidence

ORD record
ord-d003c34631f24917a62a4465e4383660
Source dataset
uspto-grants-2011_05
Patent number
US07951810B2

Reaction notes

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