Triphenylphosphine → HCID 89579814, compound

HRID 928601Notes

Reaction equation

HRID 928601 reaction equation
Br[C:2]1[C:10]2[C:9]([N:11]3[CH:16]4[CH2:17][CH2:18][CH:12]3[CH2:13][CH:14]([N:19]([CH:21]3[CH2:24][CH2:23][CH2:22]3)[CH3:20])[CH2:15]4)=[N:8][CH:7]=[N:6][C:5]=2[S:4][CH:3]=1.[CH3:25][O:26][C:27]1[C:32](B(O)O)=[CH:31][CH:30]=[CH:29][N:28]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(COC)OC.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C.C(=O)(O)[O-].[Na+].CS(C)=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:21]1([N:19]([CH3:20])[CH:14]2[CH2:13][CH:12]3[N:11]([C:9]4[C:10]5[C:2]([C:32]6[C:27]([O:26][CH3:25])=[N:28][CH:29]=[CH:30][CH:31]=6)=[CH:3][S:4][C:5]=5[N:6]=[CH:7][N:8]=4)[CH:16]([CH2:17][CH2:18]3)[CH2:15]2)[CH2:24][CH2:23][CH2:22]1

Participants

10

Reactant 3

HCID 11776TriphenylphosphineHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 89579649HCID 89579649, compound

Product 1

HCID 89579814HCID 89579814, compoundYield 36.5%

Reagents, catalysts & solvents 6

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolventHCID 516892Sodium BicarbonateSolventHCID 23503278(Methanesulfinyl)methane--water (1/1)Solvent

Conditions

Temperature
85 °C

Procedure

8-(5-Bromothieno[2,3-d]pyrimidin-4-yl)-N-cyclobutyl-N-methyl-8-azabicyclo[3.2.1]octan-3-amine (82.5 mg, 0.20 mmol) in dimethoxyethane (4 mL) and 2 M sodium carbonate solution (1 mL) was treated with (2-methoxy-3-pyridyl)boronic acid (134 mg, 0.75 mmol) and palladium (II) acetate (12 mg, 0.053 mmol), triphenylphosphine (12 mg) and the reaction was stirred in a microwave at 85° C. over 1 h. The reaction was then diluted with ethyl acetate (25 mL) and saturated aqueous sodium bicarbonate solution (25 mL) and shaken. The ethyl acetate layer was then separated, dried over sodium sulphate and concentrated in vacuum to give a gum. The gum was dissolved in DMSO/water 1:1 (2.5 mL) and purified by reverse phase HPLC. The main peak was collected and concentrated in vacuum to give N-cyclobutyl-8-[5-(2-methoxy-3-pyridyl)thieno[2,3-d]pyrimidin-4-yl]-N-methyl-8-azabicyclo[3.2.1]octan-3-amine as a gum (32 mg, 0.073 mmol, 36%). LCMS RT=4.76 min. M+1=436. 1H NMR (CDCl3) δ: 1.1 (2H, t, J=12 Hz), 1.3-1.9 (1H, m), 1.9 (3H, s), 2.2 (1H, br m), 2.9 (1H, br m), 3.9 (3H, s), 4.3 (2H, br s), 7.0 (1H, q, J=6 Hz, J′=4 Hz), 7.25 (1H, s), 7.55 (1H, d, J=6 Hz), 8.2 (1H, d, J=4 Hz), 8.5 (1H, s).

Workup

  1. stirringshaken
  2. customThe ethyl acetate layer was then separated
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated in vacuum
  5. customto give a gum
  6. custompurified by reverse phase HPLC
  7. customThe main peak was collected
  8. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-545a5456b87840d3a5ae7f1b4c660544
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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