Cesium carbonate → (R)-2-(5-cyano-6-(quinolin-6-ylamino)pyridin-2-ylamino)butanamide

HRID 2201100

Reaction equation

HRID 2201100 reaction equation
[NH2:1][C:2](=[O:27])[C@H:3]([NH:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([NH2:13])=O)=[C:9](NC2C=NC3C(C=2)=CC=CC=3)[N:8]=1)[CH2:4][CH3:5].[NH2:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[N:35]=[CH:34][CH:33]=[CH:32]2.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:11]([C:10]1[CH:14]=[CH:15][C:7]([NH:6][C@H:3]([CH2:4][CH3:5])[C:2]([NH2:1])=[O:27])=[N:8][C:9]=1[NH:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[N:35]=[CH:34][CH:33]=[CH:32]2)#[N:13]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 113736-AminoquinolineHCID 634876Binap, (A+-)-HCID 67516146(R)-6-(1-amino-1-oxobutan-2-ylamino)-2-(quinolin-3-ylamino)nicotinamide

Product 1

HCID 67775481(R)-2-(5-cyano-6-(quinolin-6-ylamino)pyridin-2-ylamino)butanamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

The mixture of (R)-2-(6-chloro-5-cyanopyridin-2-ylamino)butanamide (compound J52 in Example 203) (140 mg, 0.59 mmol), 6-aminoquinoline (260 mg, 1.8 mmol), cesium carbonate (980 mg, 3.0 mmol), BINAP (75 mg, 0.12 mmol) and Pd(OAc)2 (27 mg, 0.12 mmol) in 20 mL dioxane was degassed with Ar. The mixture was stirred under Ar at 105° C. for overnight. It was concentrated in vacuo, taken into EtOAc, washed with brine, dried, concentrated in vacuo and subjected to flash column (0 to 8% MeOH in DCM) to isolate (R)-2-(5-cyano-6-(quinolin-6-ylamino)pyridin-2-ylamino)butanamide. It was then dissolved in 4 mL DMSO. To it were added 100 mg powder K2CO3 and 2 mL 50% H2O2 in water. The mixture was stirred at RT for 1 (65 h. To it was added 4 mL water, the mixture was vigorously stirred and subjected to reverse phase preparative HPLC to isolate the title compound. (65 mg). UV: 267, 299, 330 nm. M+H found for C19H20N6O2: 365.2. NMR (CD3OD): 9.25 (1H, d, J=8.8 Hz), 9.04 (1H, d, J=2.0 Hz), 8.85 (1H, dd, J=6.4; 2.4 Hz), 8.06 (1H, d, J=9.6 Hz), 7.99 (1H, dd, J=9.2; 2.4 Hz), 7.92 (1H, m), 7.88 (1H, d, J=8.8 Hz), 6.28 (1H, d, J=9.2 Hz), 4.31 (1H, m), 2.00 (2H, m), 1.14 (3H, t, J=7.6 Hz) ppm.

Workup

  1. customwas degassed with Ar
  2. concentrationIt was concentrated in vacuo
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d39450074fea4ac2b529af920fc51896
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Linked notes

Loading…