Trifluoroacetic acid → HCID 178456061, compound

HRID 1424154Notes

Reaction equation

HRID 1424154 reaction equation
Br[C:2]1[CH:21]=[CH:20][C:5]2[NH:6][C:7]([C@@H:9]([NH:12]C(=O)OC(C)(C)C)[CH2:10][CH3:11])=[N:8][C:4]=2[CH:3]=1.[Br-].[CH2:23]([Zn+])[C:24]([CH3:27])([CH3:26])[CH3:25].O1CCCC1.FC(F)(F)C(O)=O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:23][C:24]([CH3:27])([CH3:26])[CH2:25][C:2]1[CH:21]=[CH:20][C:5]2[NH:6][C:7]([C@@H:9]([NH2:12])[CH2:10][CH3:11])=[N:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 178445880HCID 178445880, compoundHCID 178456095HCID 178456095, compound

Product 1

HCID 178456061HCID 178456061, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
140 °C

Procedure

Argon was bubbled through a mixture of (S)-tert-butyl (1-(5-bromo-1H-benzo[d]imidazol-2-yl)propyl)carbamate (Preparation 18, 150 mg, 0.42 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (48.2 mg, 0.0659 mmol), and neopentylzinc bromide in tetrahydrofuran (0.5 M, 2.5 mL, 1.3 mmol) for 5 minutes. The mixture was then heated under microwave irradiation for 10 minutes at 140° C. After cooling, the reaction was concentrated in vacuo, redissolved in dichloromethane (9 mL) and treated with trifluoroacetic acid (1 mL, 13 mmol). After stirring for 2.5 hours, the reaction was concentrated in vacuo and redissolved in a saturated solution of hydrogen chloride in methanol and stirred for 18 hours. The fully deprotected product was concentrated in vacuo and purified by preparative HPLC followed by silica gel column chromatography eluting with 0-50% CMA80/methylene chloride to afford the title compound (10 mg, 15%) as a white solid.

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction was concentrated in vacuo
  3. dissolutionredissolved in dichloromethane (9 mL)
  4. concentrationthe reaction was concentrated in vacuo
  5. dissolutionredissolved in a saturated solution of hydrogen chloride in methanol
  6. stirringstirred for 18 hours
  7. concentrationThe fully deprotected product was concentrated in vacuo
  8. custompurified by preparative HPLC
  9. washeluting with 0-50% CMA80/methylene chloride

Sources & evidence

ORD record
ord-07c89b47745c42bcb2aab966cf1e1e1c
Source dataset
uspto-grants-2015_01
Patent number
US08927587B2

Reaction notes

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