Triethylphosphine → HCID 66926083, compound

HRID 1808709Notes

Reaction equation

HRID 1808709 reaction equation
[CH3:1][Si:2]([CH3:33])([CH3:32])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2=[N:12][CH:13]=[C:14]([NH:16][NH:17][C:18]([C@H:20]3[C@H:25]([CH3:26])[CH2:24][CH2:23][N:22]([S:27]([CH2:30][CH3:31])(=[O:29])=[O:28])[CH2:21]3)=O)[N:15]=[C:10]2[CH:9]=[CH:8]1.C(N(CC)C(C)C)(C)C.C(P(CC)CC)C>>[CH2:30]([S:27]([N:22]1[CH2:23][CH2:24][C@@H:25]([CH3:26])[C@H:20]([C:18]2[N:15]3[C:14]([CH:13]=[N:12][C:11]4[N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:33])([CH3:32])[CH3:1])[CH:8]=[CH:9][C:10]=43)=[N:16][N:17]=2)[CH2:21]1)(=[O:29])=[O:28])[CH3:31]

Participants

4

Reactant 3

HCID 27365TriethylphosphineHCID 81531DiisopropylethylamineHCID 86650163HCID 86650163, compound

Product 1

HCID 66926083HCID 66926083, compoundYield 38.9%

Procedure

(+/−)-Ethanesulfonyl-trans-4-methyl-piperidine-3-carboxylic acid N′-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-hydrazide (107 mg, 0.22 mmol) was cyclized to triazolo-tricyclic product using similar conditions to those described in example 17 above [however, after over-night stirring an extra 4 equivalents of N,N-diisopropylethylamine and an extra 3 equivalents of triethylphosphine were added and the mixture was stirred an extra 6 hours before work up]. The crude product was purified by preparative TLC, eluting with 90% ethyl acetate in hexanes. The impure product was collected and purified again by preparative TLC eluting first with 3.75% methanol in methylene chloride and then a second time with 5% methanol in methylene chloride. The product band was collected to afford 41 mg of (+/−)-1-(1-ethanesulfonyl-trans-4-methyl-piperidin-3-yl)-6-(2-trimethylsilanyl-ethoxymethyl)-6H-2,3,5,6,8b-pentaaza-as-indacene as a light yellow-white powder. MS (M+H)+=479.

Workup

  1. customThe crude product was purified by preparative TLC
  2. washeluting with 90% ethyl acetate in hexanes
  3. customThe impure product was collected
  4. custompurified again by preparative TLC
  5. washeluting first with 3.75% methanol in methylene chloride
  6. customThe product band was collected

Sources & evidence

ORD record
ord-430b5479d2e04a9ea629cdfff384f0b7
Source dataset
uspto-grants-2013_01
Patent number
US08361962B2

Reaction notes

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