Morpholine → 4-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(morpholin-4-yl)pyrimidin-5-yl]-4-methyl-1,3-thiazol-2-yl}-3-methylbenzoic acid

HRID 531313Notes

Reaction equation

HRID 531313 reaction equation
[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[S:30][C:29]([C:31]5[CH:39]=[CH:38][C:34]([C:35]([OH:37])=[O:36])=[CH:33][C:32]=5[CH3:40])=[N:28][C:27]=4[CH3:41])=[CH:24][N:23]=[C:22](S(C)(=O)=O)[N:21]=3)[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1.CCN(C(C)C)C(C)C>C1COCC1>[F:47][C:2]([F:1])([F:48])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[S:30][C:29]([C:31]5[CH:39]=[CH:38][C:34]([C:35]([OH:37])=[O:36])=[CH:33][C:32]=5[CH3:40])=[N:28][C:27]=4[CH3:41])=[CH:24][N:23]=[C:22]([N:49]4[CH2:54][CH2:53][O:52][CH2:51][CH2:50]4)[N:21]=3)[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 900092914-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfonyl)pyrimidin-5-yl]-4-methyl-1,3-thiazol-2-yl}-3-methylbenzoic acid2×

Product 1

HCID 721902984-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(morpholin-4-yl)pyrimidin-5-yl]-4-methyl-1,3-thiazol-2-yl}-3-methylbenzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfonyl)pyrimidin-5-yl]-4-methyl-1,3-thiazol-2-yl}-3-methylbenzoic acid (INTERMEDIATE 54, 200 mg, 0.280 mmol) in THF (5 mL) was added morpholine (73.1 mg, 0.840 mmol) and DIEA (0.244 mL, 1.399 mmol). It was stirred at 60° C. for 15 minutes to see complete conversion by LCMS. The solvent was evaporated and the residue was purified on reverse phase HPLC, eluting with 10%-100% acetonitrile in water to give the title compound as a white solid. LCMS (M+H)+: 728.1. 1H NMR (CDCl3, 500 MHz): δ 8.33 (s, 1H), 8.08 (s, 1H), 8.02 (d, J=8.5 Hz, 1H), 7.92 (s, 1H), 7.88 (d, J=8.5 Hz, 1H), 7.77 (s, 2H), 5.75 (d, J=8.5 Hz, 1H), 4.77 (d, J=17.0 Hz, 1H), 4.36 (m, 1H), 4.086 (d, J=17.0 Hz, 1H), 3.92 (m, 4H), 3.85 (m, 4H), 2.71 (s, 3H), 2.44 (s, 3H), 0.78 (d, J=7.0 Hz, 3H). RTA IC50: 82 nM.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified on reverse phase HPLC
  3. washeluting with 10%-100% acetonitrile in water

Sources & evidence

ORD record
ord-ed8d7f830d874504b9d489127220b919
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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