Tin tetrachloride → 5-[4-(4-{[(2R)-2-Hydroxy-2-[1,2,3,4]tetraazolo[1,5-a]pyridin-6-ylethyl]amino}-1-piperidineyl)benzyl]-1,3-thiazolidine-2,4-dione

HRID 1794787Notes

Reaction equation

HRID 1794787 reaction equation
[NH2:1][CH2:2][C@@H:3]([C:5]1[CH:6]=[CH:7][C:8]2[N:9]([N:11]=[N:12][N:13]=2)[CH:10]=1)[OH:4].O=[C:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:34]=[CH:33][C:24]([CH2:25][CH:26]3[S:30][C:29](=[O:31])[NH:28][C:27]3=[O:32])=[CH:23][CH:22]=2)[CH2:17][CH2:16]1.[Sn](Cl)(Cl)(Cl)Cl>Cl.CO>[OH:4][C@H:3]([C:5]1[CH:6]=[CH:7][C:8]2[N:9]([N:11]=[N:12][N:13]=2)[CH:10]=1)[CH2:2][NH:1][CH:15]1[CH2:16][CH2:17][N:18]([C:21]2[CH:34]=[CH:33][C:24]([CH2:25][CH:26]3[S:30][C:29](=[O:31])[NH:28][C:27]3=[O:32])=[CH:23][CH:22]=2)[CH2:19][CH2:20]1

Participants

6

Reactant 3

HCID 24287Tin tetrachlorideHCID 129659555-[4-(4-Oxo-piperidin-1-yl)-benzyl]-thiazolidine-2,4-dioneHCID 69654686(1R)-2-Amino-1-[1,2,3,4]tetraazolo[1,5-a]pyridin-6-yl-1-ethanol

Product 1

HCID 865845625-[4-(4-{[(2R)-2-Hydroxy-2-[1,2,3,4]tetraazolo[1,5-a]pyridin-6-ylethyl]amino}-1-piperidineyl)benzyl]-1,3-thiazolidine-2,4-dione

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

5-[4-(4-{[(2R)-2-Hydroxy-2-[1,2,3,4]tetraazolo[1,5-a]pyridin-6-ylethyl]amino}-1-piperidinyl)benzyl]-1,3-thiazolidine-2,4-dione was prepared from (1R)-2amino-1-[1,2,3,4]tetraazolo[1,5-a]pyridin-6-yl-1-ethanol (which was obtained in Example 132) and 5-[4-(4-oxo-1-piperidinyl)benzyl]-1,3-thiazolidine-2,4-dione(which was obtained in Example 38) in substantially the same manner, as described in Example 125. The product was obtained as a yellow solid; mp: 130–132° C. This solid was dissolved in concentrated aqueous hydrochloric acid (0.3 mL) and methyl alcohol (2 mL). Tin chloride (0.196 g, 0.87 mmol) was added to the solution at room temperature. The mixture was then stirred at reflux for 2 hours. Evaporation and purification by flash column chromatography (dichloromethane/methyl alcohol 7/3)] gave a yellow solid. This solid was further purified by reverse phase HPLC to give a yellow solid (0.117 g, 61% yield); mp 182° C. (decomposed); 1H NMR (400 MHz, DMSO-d6) δ 1.90 (brs, 2 H), 2.21 (brs, 2 H), 3.03–3.36 (m, 8 H), 3.75–3.79 (m, 1 H), 4.86–4.90 (m, 1 H), 4.98–5.01 (m, 1 H), 7.03–7.05 (m, 1 H), 1.20 (brs, 4 H), 7.95–7.99 (m, 2 H), 8.21 (brs, 1 H), 9.13 (brs, 1 H), 9.45 (brs, 1 H), 12.04 (brs, 1 H), 14.13 (brs, 1 H); MS (ES) m/z: 442 (MH+).

Workup

  1. customThe product was obtained as a yellow solid
  2. temperatureat reflux for 2 hours
  3. customEvaporation and purification by flash column chromatography (dichloromethane/methyl alcohol 7/3)]
  4. customgave a yellow solid
  5. customThis solid was further purified by reverse phase HPLC

Sources & evidence

ORD record
ord-e763168932cb45918a2b2f499c3d2245
Source dataset
uspto-grants-2006_04
Patent number
US07022716B2

Reaction notes

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