Dichloromethane → 4-amino-8-(2,4-dimethoxypyrimidin-5-yl)-N-ethylcinnoline-3-carboxamide

HRID 2375672

Reaction equation

HRID 2375672 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[C:7](Br)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH3:17])=[O:14].[CH3:18][O:19][C:20]1[N:25]=[C:24]([O:26][CH3:27])[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][N:21]=1.ClCCl>C(OCC)(=O)C>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:23]3[C:24]([O:26][CH3:27])=[N:25][C:20]([O:19][CH3:18])=[N:21][CH:22]=3)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:13]([NH:15][CH2:16][CH3:17])=[O:14]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 162183882,4-Dimethoxypyrimidine-5-boronic acid pinacol ester3×HCID 672286714-Amino-8-bromo-N-ethyl-cinnoline-3-carboxamide

Product 1

HCID 251334424-amino-8-(2,4-dimethoxypyrimidin-5-yl)-N-ethylcinnoline-3-carboxamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

The title compound was prepared from 4-amino-8-bromo-N-ethyl-cinnoline-3-carboxamide (200.0 mg, 0.678 mmol) and 2,4-dimethoxyprimidine-5-boronic acid pinacol ester (363.1 mg, 1.362 mmol) according to Method B except that the reaction was heated at 90° C. to fully dissolve the starting materials. After 4 hours, additional 2,4-dimethoxyprimidine-5-boronic acid pinacol ester (363.1 mg, 1.362 mmol) was added and the reaction was refluxed overnignt. A third addition of 2,4-dimethoxyprimidine-5-boronic acid pinacol ester (363.1 mg, 1.362 mmol) and an additional 5 mol % tetrakis(triphenylphospine)palladium(0) were required to force the reaction to completion. The reaction was then worked up as described in Method B using dichloromethane rather than ethyl acetate for the extraction and crystallizing the material obtained from the flash column from chloroform/hexanes to afford the title compound as a white solid (89.5 mg, 37%). 1H NMR (300.132 MHz, CDCl3) δ 8.47 (s, 1H), 8.32 (s, 1H), 7.90 (dd, J=7.6, 2.1 Hz, 1H), 7.78-7.70 (m, 2H), 4.07 (s, 3H), 3.93 (s, 3H), 3.53 (dq, J=5.7, 7.3 Hz, 2H), 1.28 (t, J=7.3 Hz, 3H). MS APCI, m/z=354 (M+H). HPLC 2.07 min.

Workup

  1. dissolutionto fully dissolve the starting materials
  2. temperaturethe reaction was refluxed overnignt
  3. customthe reaction to completion
  4. extractionfor the extraction
  5. customcrystallizing the material

Sources & evidence

ORD record
ord-f640dd042e704a8d9faade1ec2e1bb8d
Source dataset
uspto-grants-2008_12
Patent number
US07465795B2

Linked notes

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