2-Aminothiazole → 2-biphenyl-4-yl-3-cyclopentyl-N-thiazol-2-yl-propionamide

HRID 1935188Notes

Reaction equation

HRID 1935188 reaction equation
[C:1]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:6]=[CH:5][C:4]([CH:7]([CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[C:8](O)=[O:9])=[CH:3][CH:2]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C.[NH2:57][C:58]1[S:59][CH:60]=[CH:61][N:62]=1>CN(C)C=O>[C:1]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:6]=[CH:5][C:4]([CH:7]([CH2:11][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16]2)[C:8]([NH:57][C:58]2[S:59][CH:60]=[CH:61][N:62]=2)=[O:9])=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 224679232-Biphenyl-4-yl-3-cyclopentylpropionic acid

Product 1

HCID 101775682-biphenyl-4-yl-3-cyclopentyl-N-thiazol-2-yl-propionamideYield 66.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-biphenyl-4-yl-3-cyclopentylpropionic acid (121.0 mg, 0.41 mmol), benzotriazol-1 -yloxytris(dimethylamino)phosphonium hexafluorophosphate (218.1 mg, 0.49 mmol), triethylamine (172 μL, 1.23 mmol), and 2-aminothiazole (45.3 mg, 0.45 mmol) in dry N,N-dimethylformamide (1 mL) was stirred at 25° C. under nitrogen for 24 h. The reaction mixture was concentrated in vacuo to remove N,N-dimethylformamide. The resulting residue was diluted with ethyl acetate (100 mL). The organic layer was washed with a 10% aqueous hydrochloric acid solution (1×100 mL), water (1×100 mL), and a saturated aqueous sodium chloride solution (1×100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 9/1 to 3/1 hexanes/ethyl acetate gradient elution) afforded 2-biphenyl-4-yl-3-cyclopentyl-N-thiazol-2-yl-propionamide (102.2 mg, 66%) as a white solid: mp 194-195° C.; EI-HRMS m/e calcd for C23H24N2OS (M+) 376.1609, found 376.1612.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto remove N,N-dimethylformamide
  3. additionThe resulting residue was diluted with ethyl acetate (100 mL)
  4. washThe organic layer was washed with a 10% aqueous hydrochloric acid solution (1×100 mL), water (1×100 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. washFlash chromatography (Merck Silica gel 60, 70-230 mesh, 9/1 to 3/1 hexanes/ethyl acetate gradient elution)

Sources & evidence

ORD record
ord-f9c108bc558f4ce7be45b1a7d19b707f
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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