Morpholine → HCID 59486102, compound

HRID 1972272Notes

Reaction equation

HRID 1972272 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=3)[C@H:11]([CH2:21][N:22]3[N:26]=[N:25][C:24]([CH2:27][CH2:28]O)=[N:23]3)[O:10][C:9]2=[O:30])=[CH:4][CH:3]=1.CS(Cl)(=O)=O.C(N(CC)CC)C.[NH:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=3)[C@H:11]([CH2:21][N:22]3[N:26]=[N:25][C:24]([CH2:27][CH2:28][N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)=[N:23]3)[O:10][C:9]2=[O:30])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59485822HCID 59485822, compound

Product 1

HCID 59486102HCID 59486102, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of (4S,5S)-3-(4-chlorophenyl)-5-((5-(2-hydroxyethyl)-2H-tetrazol-2-yl)methyl)-4-(3-methoxyphenyl)oxazolidin-2-one (47 mg, 0.11 mmol) in DCM is cooled to 0° C. and treated with methanesulfonyl chloride (10 μL, 0.13 mmol) followed by triethylamine (36 μL, 0.26 mmol). After 30 min., the reaction is quenched with water and extracted with DCM, then dried over Na2SO4, filtered, and concentrated to give the crude product. The crude product is then dissolved in DMF (1 mL) and treated with excess morpholine (48 μL, 0.55 mmol) and heated to 100° C. overnight. The cooled reaction is then quenched with water, basified to pH 10 and extracted with EtOAc. The crude product is purified by preparative HPLC (C-18, 10-90% ACN/water (0.05% TFA)) to give the title compound. 1H NMR (acetone-d6, 400 MHz) δ 7.47-7.43 (m, 2H), 7.34-7.29 (m, 3H), 7.04 (app t, J=2.0 Hz, 1H), 7.00-6.98 (app d, J=7.7 Hz, 1H), 6.90 (ddd, J=8.3, 2.6, 0.9 Hz, 1H), 5.61 (d, J=5.0 Hz, 1H), 5.33 (dd, J=14.6, 5.6 Hz, 1H), 5.25 (dd, J=14.6, 4.1 Hz, 1H), 4.99 (ddd, J=5.6, 5.1, 4.2 Hz, 1H), 3.78 (s, 3H), 3.55 (t, J=4.6 Hz, 4H), 2.99-2.93 (m, 2H), 2.59-2.55 (m, 2H), 2.40-2.37 (m, 4H); HPLC-MS calculated C24H27ClN6O4 (M+H+) 499.2, found 499.2.

Workup

  1. customthe reaction is quenched with water
  2. extractionextracted with DCM
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customThe cooled reaction
  8. customis then quenched with water
  9. extractionextracted with EtOAc
  10. customThe crude product is purified by preparative HPLC (C-18, 10-90% ACN/water (0.05% TFA))

Sources & evidence

ORD record
ord-c9d514c8dd304e63a915a14a08a80e64
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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