Sodium hydride → 4-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile

HRID 1499740Notes

Reaction equation

HRID 1499740 reaction equation
[H-].[Na+].[NH2:3][C:4]1[C:5]2[C:13](=[O:14])[CH:12]=[CH:11][NH:10][C:6]=2[N:7]=[CH:8][N:9]=1.[Br:15][C:16]1[C:23]([O:24][CH2:25][CH3:26])=[C:22]([CH:27](Cl)[CH3:28])[CH:21]=[C:20]([Cl:30])[C:17]=1[C:18]#[N:19]>CN(C)C=O.C(Cl)Cl>[NH2:3][C:4]1[C:5]2[C:13](=[O:14])[CH:12]=[CH:11][N:10]([CH:27]([C:22]3[CH:21]=[C:20]([Cl:30])[C:17]([C:18]#[N:19])=[C:16]([Br:15])[C:23]=3[O:24][CH2:25][CH3:26])[CH3:28])[C:6]=2[N:7]=[CH:8][N:9]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 57067884-aminopyrido[2,3-d]pyrimidin-5(8H)-oneHCID 866776672-Bromo-6-chloro-4-(1-chloroethyl)-3-ethoxybenzonitrile

Product 1

HCID 866776704-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrileYield 50%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Sodium hydride (16 mg, 0.41 mmol) was added to a mixture of 4-aminopyrido[2,3-d]pyrimidin-5(8H)-one (36 mg, 0.22 mmol) in N,N-dimethylformamide (3 mL, 40 mmol) and was stirred for 10 minutes. 2-Bromo-6-chloro-4-(1-chloroethyl)-3-ethoxybenzonitrile (Example 43, step 4) (60 mg, 0.2 mmol in N,N-dimethylformamide (2 mL) was added and the reaction was stirred at 50° C. overnight. The mixture was diluted with methylene chloride, washed with sat'd NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The product was purified by FCC eluting with CH2Cl2/MeOH (0-10%), to give 4-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile (0.04 g, 50%) as a solid, LCMS calculated for C18H15BrClN5O2 (M+H)+: m/z=450.0, 448.0; found: 450.0, 448.0.

Workup

  1. stirringthe reaction was stirred at 50° C. overnight
  2. washwashed with sat'd NaHCO3, water, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe product was purified by FCC
  7. washeluting with CH2Cl2/MeOH (0-10%)

Sources & evidence

ORD record
ord-7dafa29af22043c7b24c87a5b3731a4d
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

Loading…