4-Methylmorpholine → HCID 57959388, compound

HRID 2091444Notes

Reaction equation

HRID 2091444 reaction equation
[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]([OH:15])=O)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[N:17]1CCO[CH2:19][CH2:18]1.O[N:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[C:1]1([C:7]2[N:8]=[CH:9][C:10]([C:13]([NH:17][CH2:18][CH2:19][NH:24][C:28]3[CH:27]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:15])=[CH:11][N:12]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 7473892-Phenylpyrimidine-5-carboxylic acid2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 57959388HCID 57959388, compoundYield 72.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring mixture consisting of 2-phenylpyrimidine-5-carboxylic acid (Compound 17; synthesis described in Example 1, Steps 1-3 of WO 2007/041634 to Aldous et al., entitled “Pyrimidine Amide Compounds as PGDS Inhibitors”; 200 mg) in N,N-dimethylformamide (15 mL) was added successively N-methylmorpholine (Aldrich, 0.33 mL), N-phenethylenediamine (Acros, 173 mg), 1-hydroxybenzotriazole (209 mg), and 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (EDAC, 227 mg). The reaction mixture was stirred overnight under an argon atmosphere and was subsequently concentrated slightly under reduced pressure. The concentrate was partitioned between ethyl acetate (200 mL) and saturated aqueous sodium bicarbonate (200 mL). The layers were separated and the organic phase was washed twice with water (2×200 mL) and once with brine solution (200 mL), was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give an off-white solid. Trituration with a small amount of absolute ethanol at room temperature, collection by vacuum filtration, and suction drying afforded the title compound as a white powder (0.230 g, 72.3% yield); 1H-NMR (300 MHz; CDCl3) δ 9.13 (s, 2H), 8.51 (dd, 2H), 7.61-7.51 (m, 3H), 7.21 (t, 2H), 6.79 (t, 1H), 6.70 (d, 2H), 6.57 (broad m, 1H), 3.99 (broad m, 1H), 3.75 (m, 2H), 3.48 (t, 2H); MS (APCl+) m/z 319.

Workup

  1. concentrationwas subsequently concentrated slightly under reduced pressure
  2. customThe concentrate was partitioned between ethyl acetate (200 mL) and saturated aqueous sodium bicarbonate (200 mL)
  3. customThe layers were separated
  4. washthe organic phase was washed twice with water (2×200 mL) and once with brine solution (200 mL)
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give an off-white solid
  9. customTrituration with a small amount of absolute ethanol at room temperature, collection
  10. filtrationby vacuum filtration, and suction
  11. customdrying

Sources & evidence

ORD record
ord-0cfa5a4d220844ac94f70f95fbf71f35
Source dataset
uspto-grants-2013_05
Patent number
US08440417B2

Reaction notes

Loading…