Toluene → HCID 178453339, compound

HRID 870589Notes

Reaction equation

HRID 870589 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[CH2:48][CH2:47][C:32]2[N:33]=[C:34]([NH:37][CH:38]3[CH2:46][C:45]4[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=4)[CH2:39]3)[N:35]=[CH:36][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:56]([Si](C)(C)C)=[N+:57]=[N-:58]>CN(C)C=O.O.C(OCC)(=O)C.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[CH2:39]1[C:40]2[C:45](=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:46][CH:38]1[NH:37][C:34]1[N:35]=[CH:36][C:31]2[CH2:30][N:29]([C:27](=[O:28])[CH2:26][N:18]([CH2:14][CH2:15][C:16]3[N:56]=[N:57][NH:58][CH:17]=3)[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:48][CH2:47][C:32]=2[N:33]=1

Participants

9

Reactant 4

HCID 1140TolueneHCID 78378AzidotrimethylsilaneHCID 66586226sodium L-ascorbic acidHCID 86726552tert-butyl N-but-3-ynyl-N-[2-[2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-2-oxo-ethyl]carbamate

Product 1

HCID 178453339HCID 178453339, compoundYield 63.3%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
90 °C

Procedure

Add copper(II)sulfate pentahydrate (0.026 g; 0.2 equiv; 0.106 mmoles) and L-ascorbic acid sodium salt (0.21 g; 2.0 equiv; 1.06 mmoles) to a deoxygenated solution of tert-butyl N-but-3-ynyl-N-[2-[2-(indan-2-ylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-2-oxo-ethyl]carbamate (0.252 g; 1.0 equiv; 0.53 mmoles) in dimethylformamide (6 mL) and water (3 mL) (including toluene (0.05 mL) as an internal standard). Heat the reaction vessel to 90° C. and then add azidotrimethylsilane (0.565 mL; 8 equiv; 4.24 mmoles) slowly. Stir at 90° C. for 4 hours, then dilute the reaction mixture with water (100 mL) and ethyl acetate (50 mL), and extract 3×50 mL ethyl acetate. Wash the combined organic extracts with brine, dry 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)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-2-oxoethyl}[2-(1H-1,2,3-triazol-4-yl)-ethyl]carbamate (0.174 g; 63%) as a colorless foam: MS (m/z): 519 (M+1).

Workup

  1. extractionextract 3×50 mL ethyl acetate
  2. washWash the combined organic extracts with brine
  3. dry with materialdry 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-807e6e7eb6c84947bd27e8c3e1ad1da6
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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