Trifluoroacetic acid → HCID 49787633, compound

HRID 1615469Notes

Reaction equation

HRID 1615469 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8](Br)[C:9]([CH:19]3[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]3)=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=3)[N:6]2[N:5]=[CH:4][N:3]=1.[O:33]([C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][CH:41]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].FC(F)(F)C(O)=O>C(Cl)Cl.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.CN(C=O)C.O>[CH3:18][O:17][C:13]1[CH:12]=[C:11]([C:10]2[N:6]3[C:7]([C:2]([NH2:1])=[N:3][CH:4]=[N:5]3)=[C:8]([C:43]3[CH:44]=[CH:45][C:40]([O:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[CH:41][CH:42]=3)[C:9]=2[CH:19]2[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]2)[CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 62657Potassium Phosphate, TribasicHCID 27343774-Phenoxyphenylboronic acidHCID 66612289HCID 66612289, compound

Product 1

HCID 49787633HCID 49787633, compoundYield 32.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

The compound (25 mg, 0.050 mmol) prepared in Example 24, 4-phenoxyphenylboronic acid (10.65 mg, 0.050 mmol), potassium phosphate (10.56 mg, 0.050 mmol) and Pd(PPh3)4 (11.50 mg, 0.01 mmol) were added to a small pressure tube and DMF/water (1 mL/0.5 mL) was added. The reaction mixture was flushed with argon for 5 minutes then sealed. The reaction was heated to 100° C. for 24 hours. The DMF was removed under vacuum and the product was isolated by prep-HPLC. The product was then treated with trifluoroacetic acid (TFA) in DCM for 2 hours. The solvent (DCM/TFA) was removed under vacuum and the residue taken up in ethyl acetate/1N sodium hydroxide. The organic layer was separated and aqueous layer extracted with ethyl acetate, dried over sodium sulfate, filtered and solvent removed. Solid was dried under vacuum to obtain the title compound (8 mg) having the following physical data.

Workup

  1. customThe reaction mixture was flushed with argon for 5 minutes
  2. customthen sealed
  3. customThe DMF was removed under vacuum
  4. customthe product was isolated by prep-HPLC
  5. customThe solvent (DCM/TFA) was removed under vacuum
  6. customThe organic layer was separated
  7. extractionaqueous layer extracted with ethyl acetate
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. customsolvent removed
  11. customSolid was dried under vacuum

Sources & evidence

ORD record
ord-5fb6d3238fd54207b4b9015040223a03
Source dataset
uspto-grants-2014_07
Patent number
US08765754B2

Reaction notes

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