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 1061281Notes

Reaction equation

HRID 1061281 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-piperidineyl)benzyl]-1,3-thiazolidine-2,4-dione was prepared from (1R)-2-amino-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-piperidineyl)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, 2H), 2.21 (brs, 2H), 3.03-3.36 (m, 8H), 3.75-3.79 (m, 1H), 4.86-4.90 (m, 1H), 4.98-5.01 (m, 1H), 7.03-7.05 (m, 1H), 1.20 (brs, 4H), 7.95-7.99 (m, 2H), 8.21 (brs, 1H), 9.13 (brs, 1H), 9.45 (brs, 1H), 12.04 (brs, 1H), 14.13 (brs, 1H); 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-6d351f4ffe82474b8e322b7b523378da
Source dataset
uspto-grants-2003_02
Patent number
US06525202B2

Reaction notes

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