Acetic Acid → 5-[4-[4-((2S)-2-Hydroxy-3-phenoxy-propylamino)-piperidin-1-yl]-benzyl}-thiazolidin-2,4-dione

HRID 1794743Notes

Reaction equation

HRID 1794743 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:21]=[CH:20][C:11]([CH2:12][CH:13]3[S:17][C:16](=[O:18])[NH:15][C:14]3=[O:19])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[NH2:22][CH2:23][C@H:24]([OH:33])[CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>CN(C)C=O>[OH:33][C@H:24]([CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:23][NH:22][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:21]=[CH:20][C:11]([CH2:12][CH:13]3[S:17][C:16](=[O:18])[NH:15][C:14]3=[O:19])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1133101(2S)-(-)-1-Amino-3-phenoxy-2-propanolHCID 5049666Sodium triacetoxyborohydrideHCID 129659555-[4-(4-Oxo-piperidin-1-yl)-benzyl]-thiazolidine-2,4-dione

Product 1

HCID 101391275-[4-[4-((2S)-2-Hydroxy-3-phenoxy-propylamino)-piperidin-1-yl]-benzyl}-thiazolidin-2,4-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-{4-(4-Oxo-piperidin-1-yl)-benzyl]-thiazolidine-2,4-dione (which was obtained in Example 38) (0.15 g, 0.5 mmol) and (2S)-1-amino-3-phenoxy-propan-2-ol (which was obtained in Example 3) (0.12 g, 0.75 mmol) were mixed in N,N-dimethylformamide (15 mL) and then treated with sodium triacetoxyborohydride (0.16 g, 0.75 mmol) and acetic acid (0.045 g, 0.75 mmol). After stirring at room temperature under a nitrogen atmosphere for one day the mixture was quenched with 1N NaOH and then poured into a saturated aqueous NaHCO3. The aqueous solution was extracted with 1-butanol and the combined organic layers were concentrated. The residue was purified by preparative thin layer chromatography (10% MeOH/CH2CH2) to give the title compound as a pale yellowish solid; mp 218–220° C.; 1H NMR (300 MHz, DMSO-d6) δ 1.30–1.60 (m, 2 H), 1.80–2.00 (m, 2 H), 2.50–3.00 (m, 5 H), 3.00–3.50 (m, 3 H), 3.50–3.70 (m, 2 H), 3.85–4.00 (m, 3 H), 4.48 (dd, J=9.8, 3.8 Hz, 1 H), 6.85 (d, J=8.6 Hz, 2 H), 6.90–6.97 (m, 3 H), 7.04 (d, J=8.6 Hz, 2 H), 7.25–7.38 (m, 3 H); MS (ES) m/z: 456.0 (MH+); HRMS Calcd. for C24H29N3O4S (M+): 455.1878. Found: 455.1880.

Workup

  1. customwas quenched with 1N NaOH
  2. additionpoured into a saturated aqueous NaHCO3
  3. extractionThe aqueous solution was extracted with 1-butanol
  4. concentrationthe combined organic layers were concentrated
  5. customThe residue was purified by preparative thin layer chromatography (10% MeOH/CH2CH2)

Sources & evidence

ORD record
ord-601aa491afda43f192da77d723b80639
Source dataset
uspto-grants-2006_04
Patent number
US07022716B2

Reaction notes

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