Dimethylformamide → HCID 86665769, compound

HRID 2092562Notes

Reaction equation

HRID 2092562 reaction equation
Br[C:2]1[CH:11]=[N:10][C:9]2[C:8]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[N:7][C:6]([Cl:18])=[N:5][C:4]=2[CH:3]=1.[N:19]1[CH:24]=[C:23](B(O)O)[CH:22]=[N:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C=O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:18][C:6]1[N:7]=[C:8]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[N:10]=[CH:11][C:2]([C:23]3[CH:24]=[N:19][CH:20]=[N:21][CH:22]=3)=[CH:3][C:4]=2[N:5]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 86665768HCID 86665768, compound

Product 1

HCID 86665769HCID 86665769, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 50 mL round bottom flask, 7-bromo-2-chloro-4-morpholin-4-yl-pyrido[3,2-d]pyrimidine (120 mg, 0.0003647 mol), pyrimidine-5-boronic acid (40.4 mg, 0.0003282 mol), sodium carbonate (57.9 mg, 0.0005471 mol), DMF (5 mL) and water (3 mL) were added and the reaction vessel degassed with nitrogen for 5-10 min. To the same reaction mixture, Pd(PPh3)2Cl2 (15 mg, 0.0003 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 95° C. for 2 h. The reaction mixture was cooled and diluted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulfate. The solvent was removed under reduced pressure to afford the crude product. The crude product was purified using column chromatography (60-120 silica gel, 0-1.5% MeOH in chloroform) to yield the desired product [55 mg, 43%]. 1H NMR (300 MHz, CDCl3): δ 9.35 (s, 1H), 9.08 (s, 2H), 8.91 (d, J=2.1 Hz, 1H), 8.22 (d, J=2.7 Hz, 1H), 3.89-3.92 (m, 8H); LC-MS (ESI): Calculated mass: 328.1; Observed mass: 329.1 [M+H]+ (RT: 0.56 min).

Workup

  1. customthe reaction vessel degassed with nitrogen for 5-10 min
  2. customagain degassed with nitrogen for 5-10 min
  3. temperatureThe reaction mixture was cooled
  4. additiondiluted with ethyl acetate
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customto afford the crude product
  9. customThe crude product was purified

Sources & evidence

ORD record
ord-674efcdc3c1e4ad3a5dcc81d41d5ea55
Source dataset
uspto-grants-2013_05
Patent number
US08440662B2

Reaction notes

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