Sodium Bicarbonate → HCID 58504496, compound

HRID 2367221Notes

Reaction equation

HRID 2367221 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[N:5]=[C:4]([NH2:15])[N:3]=1.[C:16]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][C:19]=1[F:27])#[N:17].C([O-])(O)=O.[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:15][C:4]1[N:3]=[C:2]([C:21]2[CH:22]=[CH:23][C:18]([C:16]#[N:17])=[C:19]([F:27])[CH:20]=2)[CH:7]=[C:6]([N:8]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[N:5]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 31537603HCID 31537603, compound

Product 1

HCID 58504496HCID 58504496, compoundYield 66.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

In a 25 mL sealable tube under nitrogen were combined 4-chloro-6-(hexahydro-1H-azepin-1-yl)-2-pyrimidinamine (600 mg, 2.65 mmol) and (4-cyano-3-fluorophenyl)boronic acid (0.437 g, 2.65 mmol) in 1,4-dioxane (10.6 mL). Saturated aqueous NaHCO3 (2.65 mL) was added, and the resulting mixture was degassed with nitrogen for 5 minutes. Pd(Ph3P)4 (0.153 g, 0.13 mmol) was added, the vessel was sealed, and the reaction mixture was stirred overnight at 95° C. The reaction was cooled to room temperature, and the organic layer was separated and concentrated. The resulting solid was partitioned between EtOAc and water. The organic layer was separated, dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (eluent: 90/10/1 CHCl3/CH3OH/NH4OH) afforded the title compound (547 mg, 62%) as a yellow solid. LC-MS (ES) m/z=312 [M+H]+.

Workup

  1. customIn a 25 mL sealable tube under nitrogen were combined
  2. customthe resulting mixture was degassed with nitrogen for 5 minutes
  3. customthe vessel was sealed
  4. temperatureThe reaction was cooled to room temperature
  5. customthe organic layer was separated
  6. concentrationconcentrated
  7. customThe resulting solid was partitioned between EtOAc and water
  8. customThe organic layer was separated
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-71c992020387463691c86e2c7e02aaf9
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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