Trifluoroacetic acid → HCID 71539974, compound

HRID 1915953Notes

Reaction equation

HRID 1915953 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][C:11]([NH:41]C(=O)OC(C)(C)C)=[C:12]([C:14](=[O:40])[NH:15][C:16]2[CH:17]=[N:18][N:19]([CH3:39])[C:20]=2[N:21]2[CH2:27][CH2:26][CH:25]([O:28]CC3C=CC(OC)=CC=3)[CH:24]([OH:38])[CH2:23][CH2:22]2)[N:13]=1.[H][H].C(O)(C(F)(F)F)=O>CO.C(Cl)Cl.[Pd]>[NH2:41][C:11]1[S:10][C:9]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[F:8])=[N:13][C:12]=1[C:14]([NH:15][C:16]1[CH:17]=[N:18][N:19]([CH3:39])[C:20]=1[N:21]1[CH2:22][CH2:23][C@@H:24]([OH:38])[C@H:25]([OH:28])[CH2:26][CH2:27]1)=[O:40]

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 86680151HCID 86680151, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 71539974HCID 71539974, compoundYield 25.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl N-(2-(2,6-difluorophenyl)-4-((5-(4-hydroxy-5-((4-methoxyphenyl)methoxy)azepan-1-yl)-1-methyl-pyrazol-4-yl)carbamoyl)thiazol-5-yl)carbamate (0.50 g, 0.73 mmol) in MeOH (25 mL) was added 10% Pd/C (0.20 g). The mixture was stirred under a 50 psi atmosphere of hydrogen at room temperature for 18 hr. The reaction mixture was filtered through Celite® and the filtrate concentrated under reduced pressure to give a colourless solid. The crude solid was dissolved in DCM (10 mL) and TFA (10 mL) was added. The reaction mixture was stirred at room temperature for 18 hr, concentrated under reduced pressure and the crude residue was dissolved in a 1/1 mixture of MeOH/2 M aqueous NaOH (40 mL) and heated at 50° C. for 18 hr. The reaction mixture was concentrated under reduced pressure, diluted with water (30 mL) and extracted with DCM (50 mL) and EtOAc (2×50 mL). The combined organic layers were passed through a phase separation cartridge and concentrated under reduced pressure. Purification via preparative HPLC gave 490 as a pale yellow solid (86 mg, 25% over two steps). 1H NMR (400 MHz, d6-DMSO) δ 8.72-8.63 (m, 1H), 7.61-7.45 (m, 4H), 7.31-7.23 (m, 2H), 4.57 (s, 2H), 3.63 (s, 3H), 3.52 (d, J=6.5 Hz, 2H), 3.20-3.05 (m, 4H), 1.94-1.86 (m, 2H), 1.74-1.64 (m, 2H). LCMS (ES+) m/z 465 (M+1)

Workup

  1. filtrationThe reaction mixture was filtered through Celite®
  2. concentrationthe filtrate concentrated under reduced pressure
  3. customto give a colourless solid
  4. concentrationconcentrated under reduced pressure
  5. dissolutionthe crude residue was dissolved in a 1/1 mixture of MeOH/2 M aqueous NaOH (40 mL)
  6. temperatureheated at 50° C. for 18 hr
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. additiondiluted with water (30 mL)
  9. extractionextracted with DCM (50 mL) and EtOAc (2×50 mL)
  10. customThe combined organic layers were passed through a phase separation cartridge
  11. concentrationconcentrated under reduced pressure
  12. customPurification via preparative HPLC

Sources & evidence

ORD record
ord-bcb3ea1bb5114e02b43fd18601b2c6f5
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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