Trifluoroacetic acid → N4-(3-aminophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine

HRID 1482723Notes

Reaction equation

HRID 1482723 reaction equation
[F:1][C:2]1[C:3]([NH:20][C:21]2[CH:22]=[C:23]([NH:27]C(=O)OC(C)(C)C)[CH:24]=[CH:25][CH:26]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O.CCCCCCC.CCOC(C)=O>C(Cl)Cl>[NH2:27][C:23]1[CH:22]=[C:21]([NH:20][C:3]2[C:2]([F:1])=[CH:7][N:6]=[C:5]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:11][CH:10]=3)[N:4]=2)[CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 21899848Ethylacetate heptaneHCID 59174353Tert-butyl (3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)carbamate

Product 1

HCID 59174534N4-(3-aminophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamineYield 71.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)carbamate (550 mg, 1.17 mmol) in DCM (20 mL) was added TFA (2 mL). Stirred for 30 min at rt for 4 h; removed solvent via rotary evaporation and partitioned oil with cold (0° C.) saturated sodium bicarbonate (10 mL) and EtOAc (10 mL), agitated and separated layers. Organic phase was dried over sodium sulfate and the solvent was removed via rotary evaporation to give a dark oil. Flash chromatography using 20%-100% Heptane/EtOAc gradient using combiflash system gave 309 mg of a light pink solid. LC/MS (RT=2.78/(M+1)) 370.2.

Workup

  1. customremoved solvent via rotary evaporation
  2. custompartitioned oil with cold (0° C.) saturated sodium bicarbonate (10 mL) and EtOAc (10 mL)
  3. stirringagitated
  4. customseparated layers
  5. dry with materialOrganic phase was dried over sodium sulfate
  6. customthe solvent was removed via rotary evaporation
  7. customto give a dark oil

Sources & evidence

ORD record
ord-877ac81f336347e8b76da0c2adf57591
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

Loading…