Ammonia → HCID 178420868, compound

HRID 273084Notes

Reaction equation

HRID 273084 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([CH:22]4O[CH:25]=[N:24][CH:23]4S(C4C=CC(C)=CC=4)(=O)=O)[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.[NH3:37]>CCO>[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3([C:22]4[N:37]=[CH:25][NH:24][CH:23]=4)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:14][CH:15]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 68575543HCID 68575543, compound

Product 1

HCID 178420868HCID 178420868, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

The 5-{4-[4-(3-Pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-yl}-4-(toluene-4-sulfonyl)-4,5-dihydro-oxazole (500 mg) was dissolved in EtOH saturated with ammonia (7 ml) before heating in a bomb at 110° C. for 18 hours. The solvent was removed in vacuo and the residue was taken up in DCM (10 ml) and washed with saturated sodium bicarbonate solution (15 ml), followed by brine (15 ml). The organic layer was dried over Na2SO4 and concentrated in vacuo, before purifying by column chromatography, eluting with a gradient of DCM:MeOH:NH3 (from 99:1:0.1 to 90:10:1), but this failed to separate the product from a close running impurity. The residue was therefore purified using column chromatography a second time, eluting with an isocratic solution of cyclohexane:DCM:Et2O:MeOH:NH3 (10:5:3:2:0.2) to afford the title compound as a colourless solid (70 mg, 12%). 1H NMR (400 MHz, CDCl3) δ 1.8 (m, 4H), 1.93-2.05 (m, 2H), 2.24-2.39 (m, 4H), 2.57 (m, 4H), 2.63 (t, 2H), 3.67 (m, 2H), 3.79 (m, 2H), 4.00 (t, 2H), 6.77 (s, 1H), 6.81 (d, 2H), 7.18 (d, 2H), 7.38 (s, 1H). LRMS ESI+ m/z 356 [MH]+, 354 [M−H+]−.

Workup

  1. customThe solvent was removed in vacuo
  2. washwashed with saturated sodium bicarbonate solution (15 ml)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. custombefore purifying by column chromatography
  6. washeluting with a gradient of DCM
  7. customto separate the product from a close
  8. customThe residue was therefore purified
  9. washeluting with an isocratic solution of cyclohexane:DCM:Et2O:MeOH:NH3 (10:5:3:2:0.2)

Sources & evidence

ORD record
ord-16dbcae9c911463e9a8629b222ba1297
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

Loading…