3-Butyn-1-OL → 2-(but-3-yn-1-yloxy)-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]ethanone

HRID 870570Notes

Reaction equation

HRID 870570 reaction equation
[H-].[Na+].[CH2:3]([OH:7])[CH2:4][C:5]#[CH:6].Cl[CH2:9][C:10]([N:12]1[CH2:20][C:19]2[CH:18]=[N:17][C:16]([NH:21][CH:22]3[CH2:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH2:23]3)=[N:15][C:14]=2[CH2:13]1)=[O:11].C(=O)(O)[O-].[Na+]>O1CCCC1>[CH2:3]([O:7][CH2:9][C:10]([N:12]1[CH2:20][C:19]2[CH:18]=[N:17][C:16]([NH:21][CH:22]3[CH2:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH2:23]3)=[N:15][C:14]=2[CH2:13]1)=[O:11])[CH2:4][C:5]#[CH:6]

Participants

6

Reactant 4

HCID 135663-Butyn-1-OLHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 867265332-Chloro-1-[2-(indan-2-ylamino)-5,7-dihydropyrrolo[3,4-d]pyrimidin-6-yl]ethanone2×

Product 1

HCID 867265362-(but-3-yn-1-yloxy)-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]ethanoneYield 31.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
23 °C

Procedure

To sodium hydride (60 wt % in mineral oil, 2.06 g, 51.4 mmol) in tetrahydrofuran (86 mL) at 0° C., add 3-butyn-1-ol (4.64 g, 5.03 mL, 64.3 mmol), then stir at 23° C. for 15 minutes. Add this solution to 2-chloro-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]ethanone (8.45 g, 25.7 mmol) in tetrahydrofuran (86 mL) at 0° C. and stir for five minutes. Pour reaction mixture into 50% saturated aqueous sodium bicarbonate solution. Separate the organic layer and further extract the aqueous layer with ethyl ether and ethyl acetate (2×50 mL each). Combine the organic extracts and wash with brine, then dry over anhydrous sodium sulfate, filter, and concentrate. Combine the crude product with the crude product from a second reaction (run reaction under identical conditions and stoichiometry employing 2-chloro-1-[2-(indan-2-ylamino)-5,7-dihydropyrrolo[3,4-d]pyrimidin-6-yl]ethanone (3.0 g, 9.1 mmol)) and purify by silica gel column chromatography (gradient elution: 25% ethyl acetate in hexanes to 100% ethyl acetate) to give the title compound (2.90 g, 23%). MS (m/z): 363(M+1).

Workup

  1. stirringstir for five minutes
  2. additionPour
  3. customSeparate the organic layer
  4. extractionfurther extract the aqueous layer with ethyl ether and ethyl acetate (2×50 mL each)
  5. washCombine the organic extracts and wash with brine
  6. dry with materialdry over anhydrous sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate
  9. custompurify by silica gel column chromatography (gradient elution: 25% ethyl acetate in hexanes to 100% ethyl acetate)

Sources & evidence

ORD record
ord-6048563e19ad473ebb8639cbcfb74c86
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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