Potassium Phosphate, Tribasic → Methyl 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3,5-dimethylbenzoate

HRID 531258Notes

Reaction equation

HRID 531258 reaction equation
[F:1][C:2]([F:39])([F:38])[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](B4OC(C)(C)C(C)(C)O4)=[CH:24][N:23]=[C:22]([S:35][CH3:36])[N:21]=3)[C@H:14]2[CH3:37])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Br[C:41]1[CH:42]=[C:43]([C:49]2[C:58]([CH3:59])=[CH:57][C:52]([C:53]([O:55][CH3:56])=[O:54])=[CH:51][C:50]=2[CH3:60])[CH:44]=[N:45][C:46]=1[O:47][CH3:48].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[F:1][C:2]([F:39])([F:38])[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:41]4[CH:42]=[C:43]([C:49]5[C:58]([CH3:59])=[CH:57][C:52]([C:53]([O:55][CH3:56])=[O:54])=[CH:51][C:50]=5[CH3:60])[CH:44]=[N:45][C:46]=4[O:47][CH3:48])=[CH:24][N:23]=[C:22]([S:35][CH3:36])[N:21]=3)[C@H:14]2[CH3:37])[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 90009097Methyl 4-(5-bromo-6-methoxypyridin-3-yl)-3,5-dimethylbenzoate2×HCID 90009110(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[2-(methylsulfanyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-yl]methyl}-1,3-oxazolidin-2-one2×

Product 1

HCID 118021675Methyl 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3,5-dimethylbenzoate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-3-{[2-(methylthio)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-yl]methyl}-1,3-oxazolidin-2-one (INTERMEDIATE 21, 1.12 g, 1.940 mmol), methyl 4-(5-bromo-6-methoxypyridin-3-yl)-3,5-dimethylbenzoate (INTERMEDIATE 33, 0.815 g, 2.328 mmol) and Pd(Ph3P)4 (0.224 g, 0.194 mmol) were evacuated and charged with nitrogen. Added 1,4-dioxane (9.70 mL) and 2N tribasic potassium phosphate (2.91 mL, 5.82 mmol), then stirred at 170° C. for 10 minutes in a microwave reactor. LCMS showed significant product formation. The crude was purified directly by silica gel chromatography, eluting with a gradient of 5-40% ethyl acetate/hexanes over 10 column volumes to give the title compound. 1H NMR (CDCl3, 500 MHz): δ 8.36 (s, 1H), 8.07 (d, 1H), 7.89 (s, 1H), 7.81 (s, 2H), 7.74 (s, 2H), 7.33 (d, 1H), 5.73 (d, 1H), 4.81 (d, 1H), 4.44 (br, 1H), 4.08 (m, 1H), δ4.01 (s, 3H), 3.93 (s, 3H), 2.62 (s, 3H), 2.16 (s, 3H), 2.14 (s, 3H), 0.75 (d, 3H).

Workup

  1. additioncharged with nitrogen
  2. customThe crude was purified directly by silica gel chromatography
  3. washeluting with a gradient of 5-40% ethyl acetate/hexanes over 10 column volumes

Sources & evidence

ORD record
ord-b76791eeaad14583a1b4e3eb04a3de5b
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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