Ammonia → HCID 58338549, compound

HRID 445209Notes

Reaction equation

HRID 445209 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8]([C:29]1[S:33][C:32]([C:34]([OH:36])=O)=[CH:31][CH:30]=1)[CH:7]=[CH:6]2.ClCCl.C(Cl)(=O)C(Cl)=O.[NH3:46]>O1CCCC1.CCOCC.CO.CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)=[CH:16][CH:15]=1)=[C:8]([C:29]1[S:33][C:32]([C:34]([NH2:46])=[O:36])=[CH:31][CH:30]=1)[CH:7]=[CH:6]2

Participants

9

Reactant 4

HCID 222AmmoniaHCID 6344DichloromethaneHCID 65578Oxalyl chlorideHCID 58338558HCID 58338558, compound

Product 1

HCID 58338549HCID 58338549, compoundYield 80%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Add 5-(6-methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalene-2-yl)thiophene-2-carboxylic acid (86 mg, 0.2 mmol) and dichloromethane (2.4 mL) to a round bottom flask under nitrogen. Cool the suspension to 0° C. and add sequentially oxalyl chloride (22.2 μL, 0.3 mmol) and dimethylformamide (30.0 μL). Warm the resulting mixture to room temperature and stir for 30 minutes. Concentrate in vacuo to give a yellow solid. Add tetrahydrofuran (2.5 mL) to the solid. To the resulting suspension add a solution of ammonia (12.1M in water; 3 mL, 36.4 mmol) in tetrahydrofuran (5.7 mL). Stir the resulting solution for 30 minutes; then dilute with ether. Separate the layers and dry the organic layer (Na2SO4), filter and concentrate in vacuo to give a tan solid. Dissolve the resulting solid in methanol and load onto an SCX acidic ion exchange column. Flush the column with methanol then elute desired material with 2M ammonia in methanol. Concentrate the ammonia containing eluent to obtain the title compound (79 mg, 0.16 mmol) 1H NMR (d6-DMSO) δ 1.32-1.27 (m, 2H), 1.44-1.38 (m, 4H), 2.33 (s, 4H), 2.53 (t, J=5.9 Hz, 2H), 3.27 (s, 2H), 3.83 (s, 3H), 3.89 (t, J=5.9 Hz, 2H), 6.66-6.61 (m, 3H), 6.79-6.76 (m, 2H), 7.09 (dd, J=2.6, 9.2 Hz, 1H), 7.39 (d, J=2.6 Hz, 1H), 7.65-7.61 (m, 3H), 7.79 (d, J=8.8 Hz, 1H), 7.99 (d, J=8.8 Hz, 1H).

Workup

  1. temperatureWarm the resulting mixture to room temperature
  2. concentrationConcentrate in vacuo
  3. customto give a yellow solid
  4. stirringStir the resulting solution for 30 minutes
  5. customSeparate the layers
  6. dry with materialdry the organic layer (Na2SO4)
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customto give a tan solid
  10. customFlush the column with methanol
  11. washthen elute desired material with 2M ammonia in methanol
  12. concentrationConcentrate the ammonia containing eluent

Sources & evidence

ORD record
ord-f821d17e48044938b4103fdb0a2c1e0c
Source dataset
uspto-grants-2013_07
Patent number
US08476300B2

Reaction notes

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