Dimethylformamide → HCID 24962647, compound

HRID 2059573Notes

Reaction equation

HRID 2059573 reaction equation
[NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@H:12]3[C@:16]([C:18]#[CH:19])([OH:17])[C@H:15]([OH:20])[C@@H:14]([CH2:21][OH:22])[O:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.CN(C=O)C.[CH2:28](N(CC)CC)[CH3:29].C[Si](C#C)(C)C>C1COCC1.CO.N.[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>[NH2:1][C:2]1[C:3]2[C:10]([C:28]#[CH:29])=[CH:9][N:8]([C@H:12]3[C@:16]([C:18]#[CH:19])([OH:17])[C@H:15]([OH:20])[C@@H:14]([CH2:21][OH:22])[O:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

10

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 24962646HCID 24962646, compound2×

Product 1

HCID 24962647HCID 24962647, compound

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 222AmmoniaSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Alternatively, the title compound and the compounds of Examples 9 and 10 are prepared from (2R,3R,4R,5R)-2-(4-amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydrofuran-3,4-diol (Example 7). To a dried and precooled 25 ml round-bottomed flask are added (2R,3R,4R,5R)-2-(4-amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydrofuran-3,4-diol (0.060 g, 0.144 mmol), copper(I) iodide (0.006 g, 0.028 mmol), tetrakis(triphenylphosphine)palladium(0) (0.016 g, 0.014 mmol) dissolved in anhydrous THF (1.0 ml) and anhydrous DMF (0.5 ml), triethylamine (0.04 ml, 0.288 mmol), trimethylsilylacetylene (0.024 ml, 0.173 mmol). The reaction mixture is stirred at 0° C. to room temperature under argon for 30 mins. The solvent is removed in vacuo, and the residue obtained is dissolved in methanol (0.60 ml) and 30% ammonia solution (0.60 ml). The resulting reaction mixture is allowed to stir at room temperature for one hour. The solvent is removed in vacuo. The crude residue obtained is purified by reverse phase preparative HPLC on Atlantis C18 column (250×20 mm) in gradient from 5 to 95% of acetonitrile in water. Fractions containing the desired products are isolated, evaporated and lyophilized from water to give (2R,3R,4R,5R)-2-(4-amino-5-ethynyl-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydro-furan-3,4-diol (Example 8), (2R,3R,4R,5R)-2-(4-amino-5-ethynyl-pyrrolo[2,3-d]pyrimidin-7-yl)-3-buta-1,3-diynyl-5-hydroxymethyl-tetrahydro-furan-3,4-diol (Example 9), and (2R,3R,4R,5R)-2-(4-amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-3-buta-1,3-diynyl-5-hydroxymethyl-tetrahydro-furan-3,4-diol (Example 10) as white solid.

Workup

  1. customTo a dried
  2. customThe solvent is removed in vacuo
  3. customthe residue obtained
  4. customThe resulting reaction mixture
  5. stirringto stir at room temperature for one hour
  6. customThe solvent is removed in vacuo
  7. customThe crude residue obtained

Sources & evidence

ORD record
ord-c93b612939cb486890c793af4c4fdae5
Source dataset
uspto-grants-2012_10
Patent number
US08278282B2

Reaction notes

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