Water → 5-{3-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-5-chloro-6-cyano-2-ethoxyphenyl}-N,N-dimethylpyridine-2-carboxamide

HRID 1499741Notes

Reaction equation

HRID 1499741 reaction equation
[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][N:8]([CH:13]([C:15]3[CH:22]=[C:21]([Cl:23])[C:18]([C:19]#[N:20])=[C:17](Br)[C:16]=3[O:25][CH2:26][CH3:27])[CH3:14])[C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:28][N:29]([CH3:41])[C:30]([C:32]1[N:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)=[O:31].C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].O.ClCCl>>[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][N:8]([CH:13]([C:15]3[C:16]([O:25][CH2:26][CH3:27])=[C:17]([C:35]4[CH:34]=[CH:33][C:32]([C:30]([N:29]([CH3:41])[CH3:28])=[O:31])=[N:37][CH:36]=4)[C:18]([C:19]#[N:20])=[C:21]([Cl:23])[CH:22]=3)[CH3:14])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 6

HCID 962WaterHCID 6342AcetonitrileHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 53438177[6-(Dimethylcarbamoyl)pyridin-3-yl]boronic acidHCID 866776704-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile

Product 1

HCID 866776715-{3-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-5-chloro-6-cyano-2-ethoxyphenyl}-N,N-dimethylpyridine-2-carboxamideYield 24.1%

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile (20 mg, 0.04 mmol) and {6-[(dimethylamino)carbonyl]pyridin-3-yl}boronic acid (13 mg, 0.069 mmol) in acetonitrile (2 mL, 40 mmol) was added sodium carbonate (10 mg, 0.09 mmol) in water (0.5 mL, 30 mmol). The reaction was degassed with bubbling nitrogen. [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (2 mg, 0.002 mmol) was added and degassed more with N2. Reaction was heated at 100° C. for 1 h. The crude product was purified on preparative LC-MS (acetonitrile, water, TFA) to give the desired product (0.005 g, 20%) as white amorphous solid. The product was isolated as a racemic mixture. LCMS calculated for C26H24ClN7O3(M+H)+: m/z=518.1; found: 518.1.

Workup

  1. customThe reaction was degassed with bubbling nitrogen
  2. customdegassed more with N2
  3. customReaction
  4. customThe crude product was purified on preparative LC-MS (acetonitrile, water, TFA)

Sources & evidence

ORD record
ord-2a4bcf0b26e14c6694568f96841e03de
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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