Trifluoroacetic acid → HCID 67230126, compound

HRID 2408932Notes

Reaction equation

HRID 2408932 reaction equation
C(OC(=O)[NH:7][C:8]1([CH:13]([OH:23])[C:14](=[O:22])[NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH3:21])[N:17]=2)[CH2:11][CH:10]([F:12])[CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O.NC(CC1(C)CCCC1)C(N)=O.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>C(Cl)Cl.O>[NH2:7][C:8]1([CH:13]([OH:23])[C:14]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH3:21])[N:17]=2)=[O:22])[CH2:11][CH:10]([F:12])[CH2:9]1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 67229502HCID 67229502, compoundHCID 67229965HCID 67229965, compound

Product 1

HCID 67230126HCID 67230126, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent4×

Procedure

Compound 1-a (363 mg, 1.06 mmol) was treated with a 7.5 mL of a mixture of TFA:DCM:TIS:water (20:80:1:1). After 2 h at room temperature, LC/MS analysis confirmed complete removal of the Boc group and the solution was concentrated in vacuo and azeotroped with dichloromethane (3×) to remove excess TFA. The crude product (339 mg, 0.9 mmol) was dissolved in DCM (10 mL) and added to a solution of 2-amino-3-(1-methyl-cyclopentyl)-propionamide (prepared as described in Ex. 1 of WO2006/064286) (1.2 eq), PyBOP (1.2 eq) and diisopropylethylamine (4 eq) in DCM (5 mL) that had been stirred at room temperature for 5 min The mixture was stirred at room temperature until LC/MS analysis indicated complete amide formation (˜30 min) DCM was added to the reaction and the organic phase was washed with 0.1 M HCl (aq) (2×) and 10% NaHCO3 (aq) (2×). The organic phase was dried and concentrated in vacuo to afford the title compound which was used in subsequent step without further purification.

Workup

  1. customremoval of the Boc group
  2. concentrationthe solution was concentrated in vacuo
  3. customazeotroped with dichloromethane (3×)
  4. customto remove excess TFA
  5. stirringwas stirred at room temperature until LC/MS analysis
  6. additionwas added to the reaction
  7. washthe organic phase was washed with 0.1 M HCl (aq) (2×) and 10% NaHCO3 (aq) (2×)
  8. customThe organic phase was dried
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ea031ed85caa4e69815d1d3d5b869a9a
Source dataset
uspto-grants-2014_08
Patent number
US08815809B2

Reaction notes

Loading…