Triethylamine → HCID 10278997, compound

HRID 2296950Notes

Reaction equation

HRID 2296950 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)=[O:19])=[CH:13][CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH2:60]([O:62][C:63](=[O:71])[CH2:64][C:65]1[N:66]=[C:67]([NH2:70])[S:68][CH:69]=1)[CH3:61]>C(Cl)Cl>[CH2:60]([O:62][C:63](=[O:71])[CH2:64][C:65]1[N:66]=[C:67]([NH:70][C:8](=[O:9])[CH:7]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)=[O:19])=[CH:13][CH:12]=2)[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[S:68][CH:69]=1)[CH3:61]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1044544-Thiazoleacetic acid, 2-amino-, ethyl esterHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 18388776HCID 18388776, compound

Product 1

HCID 10278997HCID 10278997, compoundYield 39.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(4-[(pyridine-3-carbonyl)-amino]-phenyl}-propionic acid (prepared in Example 10, 169 mg, 0.50 mmol) in methylene chloride (10 mL) at 25° C. was treated with triethylamine (0.21 mL, 1.3 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (332 mg, 0.75 mmol), and (2-amino-thiazol-4-yl)-acetic acid ethyl ester (140 mg, 0.75 mmol). The reaction mixture was stirred at 25° C. for 20 h. At this time, the reaction was diluted with methylene chloride (50 mL). This solution was washed with a 1N aqueous hydrochloric acid solution (1×15 mL), water (1×15 mL), and a saturated aqueous sodium chloride solution (2×25 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 100% ethyl acetate) afforded [2-(3-cyclopentyl-2-{4-[(pyridine-3-carbonyl)-amino]-phenyl}-propionylamino)-thiazol-4-yl]-acetic acid ethyl ester (100.1 mg, 39.5%) as white solid: mp 195-200° C.; EI-HRMS m/e calcd for C27H30N4O4S (M+) 506.1987, found 506.1985.

Workup

  1. washThis solution was washed with a 1N aqueous hydrochloric acid solution (1×15 mL), water (1×15 mL)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e5e8153e0e9f4398916381faf7b385ca
Source dataset
uspto-grants-2002_12
Patent number
US06489485B2

Reaction notes

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