Ethane, 2-bromo-1,1-diethoxy- → 2-[4-(4-(3-pyrrolidin-1-ylpropoxy)phenyl)tetrahydro-2H-pyran-4-yl]-1,3-thiazole

HRID 272951Notes

Reaction equation

HRID 272951 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:22](=[S:24])[NH2:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:25](OC(OCC)CBr)[CH3:26]>Cl.C(O)C>[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:22]4[S:24][CH:25]=[CH:26][N:23]=4)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 866019004-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbothioamide

Product 1

HCID 115380102-[4-(4-(3-pyrrolidin-1-ylpropoxy)phenyl)tetrahydro-2H-pyran-4-yl]-1,3-thiazoleYield 16%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolvent

Procedure

4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbothioamide (150 mg, 0.43 mmol), bromoacetaldehyde diethylacetal (67 μL, 0.43 mmol), concentrated hydrochloric acid (5 drops) and ethanol were combined and heated at reflux for 5 hours. The reaction mixture was concentrated in vacuo and partitioned between 10% Na2CO3 (20 mL) and dichloromethane (2×35 mL). The combined organics were dried using Na2SO4, filtered and concentrated in vacuo. The compound was purified using column chromatography using 15 g of silica gel, eluting with dichloromethane:methanol:ammonia (95:5:0.5) to give a cream coloured solid. This was triturated with 3 mL of diethyl ether to give the title compound as a cream coloured solid (25 mg, 16%). 1H NMR (400 MHz, CD3OD) δ7.7 (s, 1H), 7.45 (s, 1H), 7.3 (d, 2H), 6.9 (d, 2H), 4.0 (t, 2H), 3.8 (m, 2H), 3.7 (m, 2H), 2.85-2.75 (m, 6H), 2.6 (m, 2H), 2.4 (m, 2H), 2.03 (m, 2H), 1.9 (m, 4H)

Workup

  1. temperatureheated
  2. temperatureat reflux for 5 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. custompartitioned between 10% Na2CO3 (20 mL) and dichloromethane (2×35 mL)
  5. customThe combined organics were dried
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe compound was purified
  9. washeluting with dichloromethane:methanol:ammonia (95:5:0.5)
  10. customto give a cream
  11. customThis was triturated with 3 mL of diethyl ether

Sources & evidence

ORD record
ord-4ea1ef07d39e4faa9ecd348562aec7cd
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

Loading…