Sodium Carbonate → 4-((4-(Isopropylamino)-5-(5-(morpholinomethyl)-1,3,4-oxadiazol-2-yl)pyridin-2-yl)amino)benzonitrile

HRID 877572Notes

Reaction equation

HRID 877572 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][CH:9]([CH3:11])[CH3:10])[C:5]([C:12]2[O:13][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[N:15][N:16]=2)=[CH:4][N:3]=1.[C:24]([C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1)#[N:25].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH:9]([NH:8][C:6]1[C:5]([C:12]2[O:13][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[N:15][N:16]=2)=[CH:4][N:3]=[C:2]([NH:30][C:29]2[CH:31]=[CH:32][C:26]([C:24]#[N:25])=[CH:27][CH:28]=2)[CH:7]=1)([CH3:11])[CH3:10]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 133964-AminobenzonitrileHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 896897432-chloro-N-isopropyl-5-(5-(morpholinomethyl)-1,3,4-oxadiazol-2-yl)pyridin-4-amine

Product 1

HCID 896907414-((4-(Isopropylamino)-5-(5-(morpholinomethyl)-1,3,4-oxadiazol-2-yl)pyridin-2-yl)amino)benzonitrile

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To solution of 2-chloro-N-isopropyl-5-(5-(morpholinomethyl)-1,3,4-oxadiazol-2-yl)pyridin-4-amine (47) (100 mg, 0.2 mmol) in dioxane (5 mL): H2O (1 mL), 4-cyano aniline (0.3 mmol, 1.1 equiv.), xanthphos (0.1 mmol, 0.5 equiv.) and Na2CO3 (0.8 mmol, 3 equiv.) were added and degassed for 10 min. To the reaction mixture Pd2(dba)3 (0.1 mmol, 0.5 equiv.) was added and degassed again for 10 min. It was then heated at 110° C. for overnight. The reaction mass was cooled and filtered through small pad of celite. The filtrate obtained was concentrated to provide crude material. The crude material was purified by column chromatography through silica gel and MeOH: DCM as eluent. The material obtained was repurified on preparative TLC to afford 4-((4-(isopropylamino)-5-(5-(morpholinomethyl)-1,3,4-oxadiazol-2-yl)pyridin-2-yl)amino)benzonitrile. 1H NMR: 400 MHz, CD3OD: δ 1.37 (d, J=6.40 Hz, 6H), 2.67 (t, J=4.8 Hz, 4H), 3.77 (t, J=4.4 Hz, 4H), 3.87 (q, J=6.4 Hz, 1H), 3.94 (s, 2H), 6.24 (s, 1H), 7.61-7.64 (m, 2H), 7.72 (d, J=6.4 Hz, 1H), 7.77-7.80 (m, 2H), 8.57 (s, 1H). LC/MS: XBridge Phe 8, 4.6×30 mm, 3.5 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 1.5 min (3.2 min run time); retention time: 1.595 min; LCMS (ES-API), m/z 420.0 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 5.964 min; Purity: 95.1%.

Workup

  1. customdegassed for 10 min
  2. customdegassed again for 10 min
  3. temperatureThe reaction mass was cooled
  4. filtrationfiltered through small pad of celite
  5. customThe filtrate obtained
  6. concentrationwas concentrated
  7. customto provide crude material
  8. customThe crude material was purified by column chromatography through silica gel and MeOH
  9. customThe material obtained
  10. customwas repurified on preparative TLC

Sources & evidence

ORD record
ord-1434974129134fbea5be249a6cdce855
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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