Morpholine → HCID 72191835, compound

HRID 531270Notes

Reaction equation

HRID 531270 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[F:7][C:8]([F:47])([F:46])[C:9]1[CH:10]=[C:11]([C@H:19]2[O:23][C:22](=[O:24])[N:21]([CH2:25][C:26]3[C:31]([C:32]4[C:33]([O:39][CH3:40])=[N:34][CH:35]=[C:36]([Cl:38])[CH:37]=4)=[CH:30][N:29]=[C:28](S(C)(=O)=O)[N:27]=3)[C@H:20]2[CH3:45])[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1>C1COCC1>[F:47][C:8]([F:7])([F:46])[C:9]1[CH:10]=[C:11]([C@H:19]2[O:23][C:22](=[O:24])[N:21]([CH2:25][C:26]3[C:31]([C:32]4[C:33]([O:39][CH3:40])=[N:34][CH:35]=[C:36]([Cl:38])[CH:37]=4)=[CH:30][N:29]=[C:28]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)[N:27]=3)[C@H:20]2[CH3:45])[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 118021482HCID 118021482, compound

Product 1

HCID 72191835HCID 72191835, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

Morpholine (0.217 mL, 2.488 mmol) was added to a THF (1 mL) solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (Step A, 311 mg, 0.498 mmol). This was then stirred for 30 minutes at 120° C. in a microwave reactor. LCMS showed >90% conversion to product. The reaction was concentrated on rotary evaporator. The crude isolate was purified by silica gel chromatography, eluting with a 0-50% isopropyl acetate/hexanes linear gradient followed by isocratic elution with 50% isopropyl acetate/hexanes for 10 minutes to give the titled compound as a white foam. LCMS (M+H)+: 632.3. 1H NMR (CDCl3, 500 MHz): δ 8.19 (d, J=2.5 Hz, 1H), 8.16 (s, 1H), 7.91 (s, 1H), 7.75 (s, 2H), 7.48 (d, J=2.5 Hz, 1H), 5.66 (d, J=8.5 Hz, 1H), 4.72 (d, J=17.1 Hz, 1H), 4.31 (m, 1H), 3.96 (s, 3H), 3.89 (m, 4H), 3.83 (m, 4H), 0.73 (d, J=6.5 Hz, 3H). SPA IC50: 671 nM.

Workup

  1. concentrationThe reaction was concentrated on rotary evaporator
  2. customThe crude isolate
  3. customwas purified by silica gel chromatography
  4. washeluting with a 0-50% isopropyl acetate/hexanes
  5. washlinear gradient followed by isocratic elution with 50% isopropyl acetate/hexanes for 10 minutes

Sources & evidence

ORD record
ord-a0a438428e4a402991010833d3bf1733
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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