Benzoyl chloride → N-(1-(1-(7-Methoxyquinolin-4-yloxy)-2-methylpropan-2-yl)-6-oxo-1,6-dihydropyridin-3-yl)benzamide

HRID 1878724Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[CH:4][C:5](=[O:25])[N:6]([C:8]([CH3:24])([CH3:23])[CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[CH:13][CH:12]=2)[CH:7]=1.CCN(C(C)C)C(C)C.[C:35](Cl)(=[O:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>C(Cl)Cl.CC(O)(C)C>[CH3:22][O:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([O:10][CH2:9][C:8]([N:6]3[C:5](=[O:25])[CH:4]=[CH:3][C:2]([NH:1][C:35](=[O:42])[C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[CH:7]3)([CH3:23])[CH3:24])=[CH:12][CH:13]=[N:14]2)=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 23 °C

Procedure

To a stirred solution of 5-amino-1-(1-(7-methoxyquinolin-4-yloxy)-2-methylpropan-2-yl)pyridin-2(1 H)-one (33 mg, 97 μmol) in CH2Cl2 (3 mL) and tBuOH (1 mL) at 0° C. under nitrogen was added DIEA (17 μl, 97 μmol) followed by a solution of benzoyl chloride (11 μl, 97 μmol) in CH2Cl2 (0.5 mL). The reaction mixture was stirred for 24 h at 23° C. and partitioned between CH2Cl2 (10 mL) and 5% NaHCO3 (5 mL). The organic was dried over MgSO4, concentrated onto dry silica, and purified on silica (12 g) eluting with 0-5% MeOH/CH2Cl2. MS (ESI pos. ion) m/z (MH+): 444. Calc'd exact mass for C26H25N3O4: 443. 1H NMR (400 MHz, Chloroform-d) 8 ppm 1.77 (s, 6 H) 3.89 (s, 3 H) 4.97 (s, 2 H) 6.15 (d, J=5.67 Hz, 1 H) 6.60 (d, J=9.59 Hz, 1H) 7.08 (dd, J=9.19, 2.54 Hz, 1 H) 7.29-7.58 (m, 8H) 7.66 (d, J=2.74 Hz, 1 H) 7.85-7.92 (m, 3 H) 8.02-8.18 (m, 2 H).

Workup

custompartitioned between CH2Cl2 (10 mL) and 5% NaHCO3 (5 mL)
dry with materialThe organic was dried over MgSO4
concentrationconcentrated onto dry silica
custompurified on silica (12 g)
washeluting with 0-5% MeOH/CH2Cl2

Sources & evidence

ORD record: ord-e7424cc85bd74b3c9f2cb427612755b5
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08314087B2

Reaction notes

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