Trimethylsilylacetylene → HCID 66618236, compound

HRID 222195Notes

Reaction equation

HRID 222195 reaction equation
I[C:2]1[C:10]2[C:9]([CH3:11])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([C@H:12]2[CH2:28][C@@H:15]3[O:16][CH:17]([C:20]4[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=4)[O:18][CH2:19][C@@H:14]3[CH2:13]2)[CH:3]=1.CCN(C(C)C)C(C)C.[C:38]([Si:40]([CH3:43])([CH3:42])[CH3:41])#[CH:39]>CN(C=O)C.[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>[CH3:27][O:26][C:23]1[CH:24]=[CH:25][C:20]([CH:17]2[O:16][C@H:15]3[CH2:28][C@H:12]([N:4]4[C:5]5[N:6]=[CH:7][N:8]=[C:9]([CH3:11])[C:10]=5[C:2]([C:39]#[C:38][Si:40]([CH3:43])([CH3:42])[CH3:41])=[CH:3]4)[CH2:13][C@H:14]3[CH2:19][O:18]2)=[CH:21][CH:22]=1

Participants

7

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 58944673HCID 58944673, compound

Product 1

HCID 66618236HCID 66618236, compoundYield 99.3%

Reagents, catalysts & solvents 3

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

Procedure

To a suspension of 5-iodo-7-[(4aS,6R,7aS)-2-(4-methoxyphenyl)-hexahydrocyclopenta[d][1,3]dioxin-6-yl]-4-methyl-7H-pyrrolo[2,3-d]pyrimidine (337 mg, 0.685 mmol), copper(I) iodide (26.0 mg, 0.137 mmol), dichlorobis(triphenylphosphine)-palladium(II) (48.0 mg, 0.0684 mmol) and DIPEA (0.240 mL, 1.38 mmol) in DMF (20.0 mL) was added ethynyltrimethylsilane (188 mg, 1.91 mmol) and the mixture was stirred at rt overnight. The reaction mixture was quenched via addition of saturated aqueous sodium bicarbonate solution and extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. Silica gel chromatography eluting with a gradient of 0 to 75% EtOAc in hexanes afforded the title compound (314 mg, 99%). LC/MS: Rt=2.38 min, ES+ 462 (AA standard).

Workup

  1. customThe reaction mixture was quenched via addition of saturated aqueous sodium bicarbonate solution
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. washSilica gel chromatography eluting with a gradient of 0 to 75% EtOAc in hexanes

Sources & evidence

ORD record
ord-551b2ed5c3964e519c12610924544430
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

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