Azidotrimethylsilane → HCID 178520884, compound

HRID 870581Notes

Reaction equation

HRID 870581 reaction equation
[Na].O=C1O[C@H]([C@H](CO)O)C(O)=C1O.[CH2:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH:15]1[NH:23][C:24]1[N:25]=[CH:26][C:27]2[CH2:33][N:32]([C:34](=[O:41])[CH2:35][CH2:36][O:37][CH2:38][C:39]#[CH:40])[CH2:31][CH2:30][C:28]=2[N:29]=1.[N:42]([Si](C)(C)C)=[N+:43]=[N-:44]>CN(C)C=O.O.C(OCC)(=O)C.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[CH2:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH:15]1[NH:23][C:24]1[N:25]=[CH:26][C:27]2[CH2:33][N:32]([C:34](=[O:41])[CH2:35][CH2:36][O:37][CH2:38][C:39]3[N:42]=[N:43][NH:44][CH:40]=3)[CH2:31][CH2:30][C:28]=2[N:29]=1

Participants

8

Reactant 3

HCID 78378AzidotrimethylsilaneHCID 66586226sodium L-ascorbic acidHCID 867265411-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-3-(prop-2-yn-1-yloxy)propan-1-one

Product 1

HCID 178520884HCID 178520884, compoundYield 44%

Reagents, catalysts & solvents 4

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

Procedure

Add copper(II) sulfate pentahydrate (0.037 g; 0.2 equiv; 0.147 mmoles) and L-ascorbic acid sodium salt (0.291 g; 2.0 equiv; 1.47 mmoles) to a solution of 1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-3-(prop-2-yn-1-yloxy)propan-1-one (0.277 g; 1.0 equiv; 0.74 mmoles) in dimethylformamide (4 mL) and water (4 mL). Evacuate the system twice and backfill with nitrogen. Add azidotrimethylsilane (0.784 mL; 8.0 equiv; 5.89 mmoles) and heat the heterogeneous mixture to 90° C. for 1 hour. Dilute the reaction mixture with water (250 mL) and ethyl acetate (50 mL) and extract with ethyl acetate (3×50 mL). Wash the combined organic extracts with brine (30 mL), dry over sodium sulfate, filter, and concentrate in vacuo to a yellow/orange oil. Purify the crude product by column chromatography (ethyl acetate to 10% methanol in ethyl acetate) to afford the desired 1-[2-(2,3-dihydro-1H-inden-2-ylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl]-3-(1H-1,2,3-triazol-4-ylmethoxy)propan-1-one (0.135 g; 44%): MS (m/z): 420 (M+1).

Workup

  1. customEvacuate the system twice
  2. extractionextract with ethyl acetate (3×50 mL)
  3. washWash the combined organic extracts with brine (30 mL)
  4. dry with materialdry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo to a yellow/orange oil
  7. customPurify the crude product by column chromatography (ethyl acetate to 10% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-d80e14cac8674ad79e55975457aeb14c
Source dataset
uspto-grants-2015_03
Patent number
US08969555B2

Reaction notes

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