Triphenylphosphine → HCID 67256262, compound

HRID 1509307Notes

Reaction equation

HRID 1509307 reaction equation
Br[C:2]1[C:13]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:23][CH2:22][CH2:21]3)=[CH:16][CH:15]=2)=[N:12][C:5]2[O:6][CH2:7][C:8](=O)[N:9]([CH3:10])[C:4]=2[CH:3]=1.[F:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F-].[Cs+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:32][C:33]1[CH:38]=[CH:37][C:36]([C:2]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:21][CH2:22][CH2:23]4)=[CH:16][CH:15]=3)=[N:12][C:5]3[O:6][CH2:7][CH2:8][N:9]([CH3:10])[C:4]=3[CH:3]=2)=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 25953Cesium fluorideHCID 2856454-Fluorophenylboronic acidHCID 86683662HCID 86683662, compound

Product 1

HCID 67256262HCID 67256262, compoundYield 23.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

In a sealed tube was added tert-butyl 1-(4-(7-bromo-1-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (82 mg, 0.168 mmol), 4-fluorophenylboronic acid (35.2 mg, 0.252 mmol), triphenylphosphine (13.21 mg, 0.05 mmol) and cesium fluoride (128 mg, 0.84 mmol) in 1,2-dimethoxyethane (2 ml). The reaction mixture was degassed by bubbling nitrogen for 10 min and palladium acetate (5.65 mg, 0.025 mmol) was added and the mixture was heated at 80° C. overnight. The reaction mixture was concentrated and the residue was diluted with ethyl acetate and the suspension was pass through silica. The filtration was concentrated and to the residue was added methanol (2.5 ml) to form a suspension. The solid was filtered and dried to give tert-butyl 1-(4-(7-(4-fluorophenyl)-1-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (19 mg). LCMS (Method D): RT=1.54 min, M+H+=504.

Workup

  1. customThe reaction mixture was degassed
  2. customby bubbling nitrogen for 10 min
  3. concentrationThe reaction mixture was concentrated
  4. additionthe residue was diluted with ethyl acetate
  5. filtrationThe filtration
  6. concentrationwas concentrated and to the residue
  7. additionwas added methanol (2.5 ml)
  8. customto form a suspension
  9. filtrationThe solid was filtered
  10. customdried

Sources & evidence

ORD record
ord-22de2a39aed24b58b120fdf5cc308272
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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