Tetrahydrofuran → Methyl 3-{3-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-4-methoxyphenyl}propanoate

HRID 1508575Notes

Reaction equation

HRID 1508575 reaction equation
[F:1][C:2]([F:33])([F:32])[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](B(O)O)=[CH:24][N:23]=[C:22]([S:29][CH3:30])[N:21]=3)[C@H:14]2[CH3:31])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.F[C:35]1[CH:36]=[C:37](N2C(C(F)(F)F)=C(C(OCC)=O)C=N2)[CH:38]=[C:39](I)[C:40]=1[O:41][CH3:42].C(=O)([O-])[O-:59].[K+].[K+].[CH2:64]1[CH2:68][O:67][CH2:66][CH2:65]1>>[F:1][C:2]([F:33])([F:32])[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:39]4[CH:38]=[C:37]([CH2:64][CH2:65][C:66]([O:67][CH3:68])=[O:59])[CH:36]=[CH:35][C:40]=4[O:41][CH3:42])=[CH:24][N:23]=[C:22]([S:29][CH3:30])[N:21]=3)[C@H:14]2[CH3:31])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 67517199Ethyl 1-(3-fluoro-5-iodo-4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate2×HCID 86704623[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]boronic acid2×

Product 1

HCID 86704617Methyl 3-{3-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-4-methoxyphenyl}propanoate

Procedure

[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]boronic acid (INTERMEDIATE 57) (200 mg, 0.404 mmol), ethyl 1-(3-fluoro-5-iodo-4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Step C, INTERMEDIATE 56) (185 mg, 0.404 mmol), potassium carbonate (0.404 ml, 0.808 mmol), 1,1bis(di-tert-butylphosphino)ferrocene palladium dichloride (27.5 mg, 0.040 mmol) and THF (5 mL) were sealed in a microwave vessel and subject to microwave irradiation at 120° C. for 30 min. Volatiles were removed under reduced pressure. The resulting pot residue was purified by preparative HPLC (reverse phase, Waters SunFire PrepC18 OBD 5 um 19×150 mm) eluting with acetonitrile/water+0.1% TFA (30% to 100% organic in 10 min, then to 100% for 2 min, 20 mL/min). Related fractions were pooled and evaporated under reduced pressure to afford a dark solid. This dark solid was further purified by preparative TLC (silica gel) developed with EtOAc/hexanes (30% ethyl acetate v/v) to give the title compound as a colorless solid foam. LCMS calc.=781.14. found=782.25 (M+H)+.

Workup

  1. customsubject to microwave irradiation at 120° C. for 30 min
  2. customVolatiles were removed under reduced pressure
  3. customThe resulting pot residue was purified by preparative HPLC (reverse phase, Waters SunFire PrepC18 OBD 5 um 19×150 mm)
  4. washeluting with acetonitrile/water+0.1% TFA (30% to 100% organic in 10 min
  5. customevaporated under reduced pressure
  6. customto afford a dark solid
  7. customThis dark solid was further purified by preparative TLC (silica gel)

Sources & evidence

ORD record
ord-1128d513efce419d8b762735d6cd4194
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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