Morpholine → HCID 25140026, compound

HRID 1669114Notes

Reaction equation

HRID 1669114 reaction equation
CS(Cl)(=O)=O.[CH2:6]([C:8]1[N:9]=[N+:10]([O-:23])[C:11]2[CH:20]=[C:19]3[C:15]([CH2:16][CH:17]([CH2:21]O)[CH2:18]3)=[CH:14][C:12]=2[N:13]=1)[CH3:7].CCN(C(C)C)C(C)C.[NH:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1>C(Cl)Cl.CN(C=O)C.CCOC(C)=O.O>[CH2:6]([C:8]1[N:9]=[N+:10]([O-:23])[C:11]2[CH:20]=[C:19]3[C:15]([CH2:16][CH:17]([CH2:21][N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)[CH2:18]3)=[CH:14][C:12]=2[N:13]=1)[CH3:7]

Participants

9

Reactant 4

HCID 8083MorpholineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 25139186HCID 25139186, compound

Product 1

HCID 25140026HCID 25140026, compoundYield 89.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulfonyl chloride (0.14 mL, 1.7 mmol) was added drop-wise to a stirred solution of alcohol 142 (347 mg, 1.42 mmol) and iPr2NEt (0.49 mL, 2.84 mmol) in DCM (25 mL) at 0° C., and the solution was stirred at 0° C. for 1 h. Water (25 mL) was added and the mixture extracted with EtOAc (3×30 mL). The organic fraction was washed with dilute Na2CO3 solution (25 mL) and water (25 mL). The organic solution was dried and the solvent evaporated to give a yellow solid, which was treated with morpholine (0.37 mL, 4.3 mmol) in DMF (10 mL) at 100-110° C. for 10 h. The solution was diluted with EtOAc (200 mL) and washed with Na2CO3 solution (50 mL) and water (30 mL). The organic solution was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (50-70%) of EtOAc/pet. ether, to give 1-oxide 143 (398 mg, 89%) as a pale yellow solid: mp (EtOAc) 111-112° C.; 1H NMR δ 8.24 (s, 1H, H-9), 7.73 (s, 1H, H-5), 3.73 (t, J=4.6 Hz, 4H, 2×CH2O), 3.19-3.29 (m, 2H, CH2), 3.02 (q, J=7.6 Hz, 2H, CH2), 2.88-2.99 (m, 2H, CH2), 2.77-2.88 (m, 1H, H-7), 2.47 (t, J=4.6 Hz, 4H, 2×CH2N), 2.38 (d, J=7.6 Hz, 2H, CH2), 1.43 (t, J=7.6 Hz, 3H, CH3); 13C NMR δ 167.1, 153.6, 147.7, 147.6, 132.3, 123.1, 114.7, 67.0 (2), 63.3, 53.9 (2), 37.6, 37.3, 36.7, 30.6, 12.3. Anal. calcd for C17H22N4O2: C, 65.0; H, 7.1; N, 17.8. Found: C, 64.9; H, 7.1; N, 17.9%.

Workup

  1. extractionthe mixture extracted with EtOAc (3×30 mL)
  2. washThe organic fraction was washed with dilute Na2CO3 solution (25 mL) and water (25 mL)
  3. customThe organic solution was dried
  4. customthe solvent evaporated
  5. customto give a yellow solid, which
  6. washwashed with Na2CO3 solution (50 mL) and water (30 mL)
  7. customThe organic solution was dried
  8. customthe solvent evaporated
  9. customThe residue was purified by chromatography
  10. washeluting with a gradient (50-70%) of EtOAc/pet. ether

Sources & evidence

ORD record
ord-c68516d51c7445f69247251f1cfc66b2
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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