2-Aminothiazole → HCID 10114125, compound

HRID 2296934Notes

Reaction equation

HRID 2296934 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:25])[CH2:19][C:20]3[S:21][CH:22]=[CH:23][CH:24]=3)=[CH:13][CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]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.[NH2:53][C:54]1[S:55][CH:56]=[CH:57][N:58]=1.C(N(CC)CC)C>C(Cl)Cl.O>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:25])[CH2:19][C:20]3[S:21][CH:22]=[CH:23][CH:24]=3)=[CH:13][CH:12]=2)[C:8]([NH:53][C:54]2[S:55][CH:56]=[CH:57][N:58]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 21552-AminothiazoleHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 18388775HCID 18388775, compound

Product 1

HCID 10114125HCID 10114125, compoundYield 89.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-[4-(2-thiophen-2-yl-acetylamino)-phenyl]-propionic acid (76.6 mg, 0.21 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (142.0 mg, 0.32 mmol) and 2-aminothiazole (32.1 mg, 0.32 mmol) in methylene chloride (1 mL) at 25° C. was treated with triethylamine (0.9 mL, 0.64 mmol). The reaction mixture was stirred at 25° C. for 16 h. This mixture was then poured into water (50 mL) and extracted with methylene chloride (2×25 mL). The combined organic extracts were washed with a 1N aqueous sodium hydroxide solution (1×25 mL), a 1N aqueous hydrochloric acid solution (1×25 mL), water (1×25 mL), and a saturated aqueous sodium chloride solution (3×25 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 60/40 hexanes/ethyl acetate) afforded 3-cyclopentyl-N-thiazol-2-yl-2-[4-(2-thiophen-2-yl-acetylamino)-phenyl]-propionamide (82.7 mg, 87.8%) as a tan solid: mp 220-221° C.; EI-HRMS m/e calcd for C23H25N3O2S2 (M+) 4391388, found 439.1379.

Workup

  1. extractionextracted with methylene chloride (2×25 mL)
  2. washThe combined organic extracts were washed with a 1N aqueous sodium hydroxide solution (1×25 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-08a8ca84198f48c4b7d68f946c4c74f2
Source dataset
uspto-grants-2002_12
Patent number
US06489485B2

Reaction notes

Loading…