Binap, (A+-)- → HCID 10116443, compound

HRID 1392979Notes

Reaction equation

HRID 1392979 reaction equation
CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[NH2:53][C:54]1[N:59]=[C:58]([C:60]2[N:64]3[CH:65]=[CH:66][CH:67]=[CH:68][C:63]3=[N:62][CH:61]=2)[CH:57]=[CH:56][N:55]=1.Br[C:70]1[CH:89]=[CH:88][C:73]([C:74]([C:76]2[CH:81]=[CH:80][C:79]([N:82]3[CH2:87][CH2:86][O:85][CH2:84][CH2:83]3)=[CH:78][CH:77]=2)=[O:75])=[CH:72][CH:71]=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:85]1[CH2:84][CH2:83][N:82]([C:79]2[CH:78]=[CH:77][C:76]([C:74]([C:73]3[CH:88]=[CH:89][C:70]([NH:53][C:54]4[N:59]=[C:58]([C:60]5[N:64]6[CH:65]=[CH:66][CH:67]=[CH:68][C:63]6=[N:62][CH:61]=5)[CH:57]=[CH:56][N:55]=4)=[CH:71][CH:72]=3)=[O:75])=[CH:81][CH:80]=2)[CH2:87][CH2:86]1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 691978644-(Imidazo[1,2-a]pyridin-3-yl)pyrimidin-2-amineHCID 69200079HCID 69200079, compound

Product 1

HCID 10116443HCID 10116443, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Procedure

A mixture of sodium tert-butoxide (31 mg, 0.32 mmol), palladium acetate (3 mg, 0.013 mmol), and (S)-BINAP (11 mg, 0.018 mmol) in toluene (2 mL) was stirred at room temperature for 0.5 h. A warm suspension of 2-amino-4-(imidazo[1,2-a]pyridin-3-yl)pyrimidine (58 mg, 0.27 mmol) in toluene (4 mL) and 4-bromo-4′-morpholinobenzophenone (79 mg, 0.23 mmol) was added, and the mixture was heated at 100° C. for 4 h. The solvent was removed in vacuo, and the residue was partitioned between dichloromethane and water. The phases were separated and the organic layer was washed with brine, dried (MgSO4) and the solvent was removed in vacuo. The crude product was purified by column chromatography on silica gel using chloroform/ethanol, 98:2, as the eluent affording 25 mg (23% yield) of the title compound as a yellow solid: mp (decomp.) >237° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.18 (d, J=6.8 Hz, 1 H), 10.1 (s, 1 H), 8.68 (s, 1 H), 8.53 (d, J=5.4 Hz, 1 H), 7.96 (d, J=8.5 Hz, 2 H), 7.80 (d, J=8.9 Hz, 1 H), 7.73 (d, J=8.6 Hz, 2 H), 7.69 (d, J=8.7 Hz, 2 H), 7.56-7.51 (m, 2 H), 7.19 (t, J=6.8 Hz, 1 H), 7.05 (d, J=8.7 Hz, 2 H), 3.76 (s, 4 H), 3.33 (s, 4 H); 13C NMR (400 MHz, DMSO-d6) δ 193.0, 159.4, 157.6, 157.3, 153.9, 148.3, 144.3, 139.3, 131.9, 131.1, 131.0, 129.7, 127.5, 127.4, 121.3, 118.2, 117.7, 114.2, 113.3, 108.4, 66.2, 47.2; MS (TSP) 7 m/z 477 (M+1).

Workup

  1. additionwas added
  2. temperaturethe mixture was heated at 100° C. for 4 h
  3. customThe solvent was removed in vacuo
  4. customthe residue was partitioned between dichloromethane and water
  5. customThe phases were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent was removed in vacuo
  9. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-5751aa1f0f374f3092305caf3ab1a935
Source dataset
uspto-grants-2008_03
Patent number
US07345050B2

Reaction notes

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