Toluene → HCID 178453340, compound

HRID 870597Notes

Reaction equation

HRID 870597 reaction equation
[Na].O=C1O[C@H]([C@H](CO)O)C(O)=C1O.[CH2:14]([N:18]([CH2:26][C:27]([N:29]1[CH2:37][C:36]2[CH:35]=[N:34][C:33]([NH:38][CH:39]3[CH2:47][C:46]4[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=4)[CH2:40]3)=[N:32][C:31]=2[CH2:30]1)=[O:28])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:15][C:16]#[CH:17].C1(C)C=CC=CC=1.[N:55]([Si](C)(C)C)=[N+:56]=[N-:57]>CN(C)C=O.O.C(OCC)(=O)C.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[CH2:40]1[C:41]2[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:47][CH:39]1[NH:38][C:33]1[N:34]=[CH:35][C:36]2[CH2:37][N:29]([C:27](=[O:28])[CH2:26][N:18]([CH2:14][CH2:15][C:16]3[NH:57][N:56]=[N:55][CH:17]=3)[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:30][C:31]=2[N:32]=1

Participants

9

Reactant 4

HCID 1140TolueneHCID 78378AzidotrimethylsilaneHCID 66586226sodium L-ascorbic acidHCID 86726563HCID 86726563, compound

Product 1

HCID 178453340HCID 178453340, compoundYield 70.7%

Reagents, catalysts & solvents 4

HCID 24463Copper sulfate pentahydrateCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Add copper(II)sulfate pentahydrate (0.022 g; 0.2 equiv; 0.088 mmoles) and L-ascorbic acid sodium salt (0.175 g; 2.0 equiv; 0.88 mmoles) to a deoxygenated solution of tert-butyl N-but-3-ynyl-N-[2-[2-(indan-2-ylamino)-5,7-dihydropyrrolo[3,4-d]pyrimidin-6-yl]-2-oxo-ethyl]carbamate (0.204 g; 1.0 equiv; 0.44 mmoles) in dimethylformamide (6 mL) and water (3 mL) (including toluene (0.05 mL) as an internal standard). Heat to 90° C. and then add azidotrimethylsilane (0.47 mL; 8 equiv; 3.54 mmoles) dropwise with continued stirring at 90° C. Stir for 3 hours, then dilute the reaction mixture with water (100 mL) and ethyl acetate (50 mL). Extract with ethyl acetate (3×50 mL), and wash the combined organic extracts with brine. Dry the organics over magnesium sulfate, filter, and concentrate. Purify the crude product by column chromatography (0 to 10% methanol in ethyl acetate) to give tert-butyl {2-[2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]-2-oxoethyl}[2-(1H-1,2,3-triazol-5-yl)ethyl]carbamate (0.157 g; 70%) as a yellowish foam: MS (m/z): 505(M+1).

Workup

  1. extractionExtract with ethyl acetate (3×50 mL)
  2. washwash the combined organic extracts with brine
  3. dry with materialDry the organics over magnesium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the crude product by column chromatography (0 to 10% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-3aa247614f0348fab0a2af226df7aa6f
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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