3-Aminobiphenyl → HCID 90041773, compound

HRID 530395Notes

Reaction equation

HRID 530395 reaction equation
[CH2:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[CH2:4][CH2:3][N:2]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].Cl[C:19]1[N:24]=[C:23](Cl)[C:22]([C:26]#[N:27])=[CH:21][N:20]=1.CCN(C(C)C)C(C)C.[C:37]1([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH:42]=[CH:41][CH:40]=[C:39]([NH2:43])[CH:38]=1>C(Cl)Cl.C(OCC)(=O)C>[C:37]1([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH:42]=[CH:41][CH:40]=[C:39]([NH:43][C:19]2[N:24]=[C:23]([N:8]3[CH2:7][CH2:6][C:5]4([CH2:1][N:2]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:3][CH2:4]4)[CH2:10][CH2:9]3)[C:22]([C:26]#[N:27])=[CH:21][N:20]=2)[CH:38]=1

Participants

7

Reactant 4

HCID 167173-AminobiphenylHCID 81531DiisopropylethylamineHCID 140269072,4-Dichloro-5-cyanopyrimidineHCID 34178604tert-Butyl 2,8-diazaspiro[4.5]decane-2-carboxylate

Product 1

HCID 90041773HCID 90041773, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (69 mg, 0.287 mol) was added to a cooled solution of the 2,4-dichloropyrimidine-5-carbonitrile (50 mg, 0.287 mmol) and Hunig's base (50 uL, 0.287 mmol) in CH2Cl2 (1.5 mL) and the reaction mixture was stirred for 3 hours at 0° C. The solvent was removed under reduced pressure, then the mixture was diluted with CH3CN (2 mL) and the biphenyl-3-amine (97 mg, 0.575 mol) was added. The mixture was then heated to 80° C. overnight. Upon cooling, the reaction mixture was diluted with ethyl acetate, washed with H2O and then brine and the organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) provided a mixture of the two possible isomers which was separated by the reverse phase chromatography to afford tert-butyl 8-[2-(biphenyl-3-ylamino)-5-cyanopyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-2-carboxylate. MS ESI calcd. for C30H35N6O2 [M+H]+ 511, found 511.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe mixture was diluted with CH3CN (2 mL)
  3. temperatureThe mixture was then heated to 80° C. overnight
  4. temperatureUpon cooling
  5. washwashed with H2O
  6. dry with materialbrine and the organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (ethyl acetate/hexanes)
  10. customprovided
  11. additiona mixture of the two possible isomers which
  12. customwas separated by the reverse phase chromatography

Sources & evidence

ORD record
ord-c7160d988a0b493897c309bdf1881920
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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