Acetic Acid → 5-{4-[4-((2S)-2-Hydroxy-3-phenoxy-propylamino)-piperidin-1-yl]-benzylidene}-2-thioxo-thiazolidin-4-one

HRID 1061239Notes

Reaction equation

HRID 1061239 reaction equation
[O:1]=[C:2]1[C:6](=[CH:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]3)=[CH:10][CH:9]=2)[S:5][C:4](=[S:21])[NH: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>ClCCCl>[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:17]1[CH2:18][CH2:19][N:14]([C:11]2[CH:12]=[CH:13][C:8]([CH:7]=[C:6]3[S:5][C:4](=[S:21])[NH:3][C:2]3=[O:1])=[CH:9][CH:10]=2)[CH2:15][CH2:16]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1133101(2S)-(-)-1-Amino-3-phenoxy-2-propanolHCID 5049666Sodium triacetoxyborohydrideHCID 731782011-[4-(4-Oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-phenyl]-piperidin-4-one

Product 1

HCID 865845495-{4-[4-((2S)-2-Hydroxy-3-phenoxy-propylamino)-piperidin-1-yl]-benzylidene}-2-thioxo-thiazolidin-4-one

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-[4-(4-Oxo-2-thioxo-thiazolidin-5-ylidenemethyl)-phenyl]-piperidine-4-one (which was obtained in Example 34) (0.16 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 1,2-dichloroethane (10 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 sodium hydroxide (NaOH) and then poured into a saturated aqueous sodium bicarbonate (NaHCO3). The aqueous layer was extracted with dichloromethane and the combined organic layers were dried and concentrated. The residue was purified by preparative thin layer chromatography (16% MeOH/CH2CH2) to give the title compound as a pale yellowish solid; mp >220° C. (decomposed); 1H NMR (300 MHz, DMSO-d6) δ 1.50-1.70 (m, 2H), 1.90-2.10 (m, 2H), 2.60-3.40 (m, 7H), 3.90-4.20 (m, 3H), 6.70-7.15 (m, 6H), 7.30 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.8 Hz, 2H); MS (ES) m/z: 470.0 (MH+); HRMS Calcd. for C24H27N3O3S2 (M+): 469.1494. Found: 469.1488.

Workup

  1. customwas quenched with 1N sodium hydroxide (NaOH)
  2. additionpoured into a saturated aqueous sodium bicarbonate (NaHCO3)
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. customthe combined organic layers were dried
  5. concentrationconcentrated
  6. customThe residue was purified by preparative thin layer chromatography (16% MeOH/CH2CH2)

Sources & evidence

ORD record
ord-e3a4e7c47184439d856450c639fe4888
Source dataset
uspto-grants-2003_02
Patent number
US06525202B2

Reaction notes

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