Sodium Carbonate → 4-{2-Amino-6-[(1,1-dimethyl-2-phenylethyl)amino]-4-pyrimidinyl}-2-fluorobenzonitrile

HRID 2367261Notes

Reaction equation

HRID 2367261 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH:9][C:10]([CH3:19])([CH3:18])[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:3]=1.[F:20][C:21]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[CH:25][C:22]=1[C:23]#[N:24].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[NH2:8][C:6]1[N:7]=[C:2]([C:27]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[C:21]([F:20])[CH:28]=2)[CH:3]=[C:4]([NH:9][C:10]([CH3:19])([CH3:18])[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:5]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 513509512-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 866591756-Chloro-N4-(1,1-dimethyl-2-phenylethyl)-2,4-pyrimidinediamine

Product 1

HCID 669915204-{2-Amino-6-[(1,1-dimethyl-2-phenylethyl)amino]-4-pyrimidinyl}-2-fluorobenzonitrileYield 47.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 6-chloro-N4-(1,1-dimethyl-2-phenylethyl)-2,4-pyrimidinediamine (338 mg, 1.22 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (452 mg, 1.83 mmol), Pd(PPh3)4 (139 mg, 0.12 mmol) and Na2CO3 (323 mg, 3.05 mmol) in 1,4-dioxane (6 mL) and water (2 mL) was stirred and heated at 140° C. for 30 min in a Biotage Initiator microwave synthesizer. The reaction mixture was cooled to room temperature and concentrated to dryness, and the resulting residue was partitioned between EtOAc and water. The aqueous layer was extracted by EtOAc (3×50 mL), and the combined organic layers were dried over Na2SO4, filtered and concentrated to dryness. Purification by RPHPLC with CH3CN in water (0.01% ammonium hydrogen carbonate) (gradient: from 70% to 80% in 7.5 min, flow rate: 30 mL/min), afforded the title compound (210 mg) as a white solid. LC-MS (ES) m/z=362 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated to dryness
  3. customthe resulting residue was partitioned between EtOAc and water
  4. extractionThe aqueous layer was extracted by EtOAc (3×50 mL)
  5. dry with materialthe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customPurification by RPHPLC with CH3CN in water (0.01% ammonium hydrogen carbonate) (gradient: from 70% to 80% in 7.5 min, flow rate: 30 mL/min)

Sources & evidence

ORD record
ord-b19f1fa0431947c69a0440c287b82853
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…