Tetrahydrofuran → (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-(5-isopropyl-2-methoxypyridin-3-yl)-2-(morpholin-4-yl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 531274Notes

Reaction equation

HRID 531274 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C1COCC1.[F:12][C:13]([F:54])([F:53])[C:14]1[CH:15]=[C:16]([C@H:24]2[O:28][C:27](=[O:29])[N:26]([CH2:30][C:31]3[C:36]([C:37]4[C:38]([O:46][CH3:47])=[N:39][CH:40]=[C:41]([CH:43]([CH3:45])[CH3:44])[CH:42]=4)=[CH:35][N:34]=[C:33](S(C)(=O)=O)[N:32]=3)[C@H:25]2[CH3:52])[CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=1.C(#N)C.O>CC#N>[F:22][C:20]([F:21])([F:23])[C:18]1[CH:17]=[C:16]([C@H:24]2[O:28][C:27](=[O:29])[N:26]([CH2:30][C:31]3[C:36]([C:37]4[C:38]([O:46][CH3:47])=[N:39][CH:40]=[C:41]([CH:43]([CH3:45])[CH3:44])[CH:42]=4)=[CH:35][N:34]=[C:33]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)[N:32]=3)[C@H:25]2[CH3:52])[CH:15]=[C:14]([C:13]([F:12])([F:54])[F:53])[CH:19]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8083MorpholineHCID 18373917Acetonitrile--water (1/1)HCID 90009173(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-(5-isopropyl-2-methoxypyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one2×

Product 1

HCID 72192438(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-(5-isopropyl-2-methoxypyridin-3-yl)-2-(morpholin-4-yl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

Morpholine (0.062 mL, 0.711 mmol) was added to a THF (1 mL) solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-(5-isopropyl-2-methoxypyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 17, 90 mg, 0.142 mmol) in a microwave vial. The vial was capped, then heated for 15 minutes at 90° C. in a BIOTAGE microwave reactor. LCMS showed complete conversion to product. The reaction was diluted with 2 mL CH3CN and loaded directly onto an X-Bridge 21.2×150 mm RP column. Using a 10-100% acetonitrile/water (0.1% NH4OH) linear gradient at 15 mL/minutes over 20 minutes, the product of interest was recovered and lyophilized to give the titled compound as a white solid. LCMS (M+H)+: 640.5. 1H NMR (CDCl3, 500 MHz): δ 8.17 (s, 1H), 8.10 (d, J=2.2 Hz, 1H), 7.91 (s, 1H), 7.75 (s, 2H), 7.35 (d, J=2.2 Hz, 1H), 5.64 (d, J=8.5 Hz, 1H), 4.72 (d, J=17.1 Hz, 1H), 4.32 (m, 1H), 4.00 (d, J=17.2 Hz, 1H), 3.94 (s, 3H), 3.88 (m, 4H), 3.83 (m, 4H), 2.96 (m, 1H), 1.29 (d, J=7.0 Hz, 6H), 0.71 (d, J=6.5 Hz, 3H). SPA IC50: 229 nM.

Workup

  1. customThe vial was capped
  2. customover 20 minutes
  3. customthe product of interest was recovered

Sources & evidence

ORD record
ord-4ff411ce63e043fea378f7d4d3541510
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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