Potassium Phosphate, Tribasic → HCID 56971593, compound

HRID 1508606Notes

Reaction equation

HRID 1508606 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@H:12]2[O:16][C:15](=[O:17])[N:14]([CH2:18][C:19]3[C:24]([C:25]4[CH:30]=[C:29]([CH:31]([CH3:33])[CH3:32])[C:28]([F:34])=[CH:27][C:26]=4[O:35][CH3:36])=[CH:23][N:22]=[C:21]([N:37]4[CH2:40][CH:39]([F:41])[CH2:38]4)[N:20]=3)[C@H:13]2[CH3:42])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:51]1(B(O)O)[CH2:53][CH2:52]1>O1CCOCC1.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>[CH:51]1([C:2]2[CH:3]=[C:4]([C@H:12]3[O:16][C:15](=[O:17])[N:14]([CH2:18][C:19]4[C:24]([C:25]5[CH:30]=[C:29]([CH:31]([CH3:32])[CH3:33])[C:28]([F:34])=[CH:27][C:26]=5[O:35][CH3:36])=[CH:23][N:22]=[C:21]([N:37]5[CH2:38][CH:39]([F:41])[CH2:40]5)[N:20]=4)[C@H:13]3[CH3:42])[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=2)[CH2:53][CH2:52]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 86704653HCID 86704653, compound

Product 1

HCID 56971593HCID 56971593, compoundYield 46.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To (4S,5R)-5-[3-bromo-5-(trifluoromethyl)phenyl]-3-({2-(3-fluoroazetidin-1-yl)-5-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]pyrimidin-4-yl}methyl)-4-methyl-1,3-oxazolidin-2-one (0.031 g, 0.047 mmol) in dioxane (0.5 mL) was added tripotassium phosphate (0.071 mL, 0.142 mmol), cyclopropylboronic acid (6.10 mg, 0.071 mmol) and tetrakis(triphenylphosphine)palladium(0) (5.47 mg, 4.74 μmol). The system was flushed with nitrogen and was sealed before heating at 140° C. by microwave irradiation for 30 minutes. The reaction mixture was diluted with EtOAc, washed with sat. aqueous sodium bicarbonate, water and brine. The organic phase was dried over sodium sulfate, filtered, concentrated and the crude was purified by column chromatography to yield (4S,5R)-5-[3-cyclopropyl-5-(trifluoromethyl)phenyl]-3-({2-(3-fluoroazetidin-1-yl)-5-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]pyrimidin-4-yl}methyl)-4-methyl-1,3-oxazolidin-2-one (13.3 mg, 0.022 mmol) as white solid. LCMS calc.=617.3. found=617.5.1H NMR (CDCl3, 500 MHz) δ 8.15 (s, 1H), 7.29 (d, J=7.5 Hz, 2H), 7.19 (s, 1H), 7.01 (d, J=8.5 Hz, 1H), 6.69 (d, J=12 Hz, 1H), 5.54˜5.33 (br m, 2H), 4.74 (d, J=17 Hz, 1H), 4.50 (m, 2H), 4.33 (m, 3H), 4.16˜4.15 (br m, 1H), 3.97˜3.94 (br m, 1H), 3.79 (s, 3H), 3.25˜3.19 (m, 1H), 1.31˜1.26 (m, 6H), 1.07 (m, 2H), 0.76 (m, 2H), 0.69 (m, 3H). RTA=98 nM.

Workup

  1. customThe system was flushed with nitrogen
  2. customwas sealed
  3. additionThe reaction mixture was diluted with EtOAc
  4. washwashed with sat. aqueous sodium bicarbonate, water and brine
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe crude was purified by column chromatography

Sources & evidence

ORD record
ord-84a57e52f7264e0b83d34ed2d34ee883
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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