Hexane → (4S,6S)-4-(2-fluoro-5-(6-((trimethylsilyl)ethynyl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

HRID 930325Notes

Reaction equation

HRID 930325 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[CH:15]=[CH:14][C:13](B2OC(C)(C)C(C)(C)O2)=[CH:12][C:11]=1[C@:25]1([CH2:36][F:37])[CH2:30][C@@H:29]([C:31]([F:34])([F:33])[F:32])[O:28][C:27]([NH2:35])=[N:26]1.Br[C:39]1[CH:40]=[CH:41][C:42]([C:45]#[C:46][Si:47]([CH3:50])([CH3:49])[CH3:48])=[N:43][CH:44]=1.CCCCCC>O1CCOCC1.O.O.C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C>[F:9][C:10]1[CH:15]=[CH:14][C:13]([C:39]2[CH:44]=[N:43][C:42]([C:45]#[C:46][Si:47]([CH3:48])([CH3:50])[CH3:49])=[CH:41][CH:40]=2)=[CH:12][C:11]=1[C@:25]1([CH2:36][F:37])[CH2:30][C@@H:29]([C:31]([F:33])([F:32])[F:34])[O:28][C:27]([NH2:35])=[N:26]1

Participants

8

Reactant 4

HCID 8058HexaneHCID 62657Potassium Phosphate, TribasicHCID 109995845-Bromo-2-[2-(trimethylsilyl)ethynyl]pyridineHCID 86732145(4S,6S)-4-(2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

Product 1

HCID 86732153(4S,6S)-4-(2-fluoro-5-(6-((trimethylsilyl)ethynyl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amineYield 44.3%

Reagents, catalysts & solvents 3

HCID 178482226HCID 178482226, compoundCatalystHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A mixture of potassium phosphate (0.676 g, 3.19 mmol), (4S,6S)-4-(2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (8b, 1.428 g, 3.40 mmol), 5-bromo-2-((trimethylsilyl)ethynyl)pyridine (0.270 g, 1.062 mmol) and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(II) chloride (0.038 g, 0.053 mmol) in dioxane/water (5.0/1.2 mL) was heated in microwave reactor at 110° C. for 35 min. The reaction mixture was diluted with water and extracted with DCM three times. The combined organic layers were washed with brine, dried on sodium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography: 0-100% EtOAc/hexane in 15 min. The product was obtained as an off-white solid. Trituration with hexane afforded the pure product as a white solid (0.22 g, 44% yield). MS m/z=468 [M+H]+. Calculated for C22H22F5N3OSi: 467.5.

Workup

  1. extractionextracted with DCM three times
  2. washThe combined organic layers were washed with brine
  3. customdried on sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by silica gel chromatography
  7. customThe product was obtained as an off-white solid

Sources & evidence

ORD record
ord-ded940f4a1494d38a1b5cccb9afe27b6
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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