2-Aminothiazole → 3-cyclopentyl-2-[4-(3-dimethylamino-prop-1-ynyl)-phenyl]-N-thiazol-2-yl-propionamide

HRID 1936255Notes

Reaction equation

HRID 1936255 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[C:18][CH2:19][N:20]([CH3:22])[CH3:21])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[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.C(N(CC)CC)C.[NH2:57][C:58]1[S:59][CH:60]=[CH:61][N:62]=1>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[C:18][CH2:19][N:20]([CH3:22])[CH3:21])=[CH:13][CH:12]=2)[C:8]([NH:57][C:58]2[S:59][CH:60]=[CH:61][N:62]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 224652993-Cyclopentyl-2-[4-(3-dimethylamino-prop-1-ynyl)-phenyl]-propionic acid

Product 1

HCID 101344673-cyclopentyl-2-[4-(3-dimethylamino-prop-1-ynyl)-phenyl]-N-thiazol-2-yl-propionamideYield 19.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3-cyclopentyl-2-[4-(3-dimethylamino-prop-1-ynyl)-phenyl]-propionic acid (150 mg, 0.50 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (332 mg, 0.75 mmol), triethylamine (0.21 mL, 1.50 mmol) and 2-aminothiazole (86 mg, 0.86 mmol) in methylene chloride (5 mL) was stirred at 25° C. for 2 h. At this time, the reaction was diluted with methylene chloride (10 mL). This solution was washed with water (1×10 mL), a 1N aqueous sodium hydroxide solution (1×10 mL), and a half-saturated aqueous sodium chloride solution (1×10 mL). The aqueous layers were back extracted with methylene chloride (1×10 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 95/5 methylene chloride/methanol) afforded 3-cyclopentyl-2-[4-(3-dimethylamino-prop-1-ynyl)-phenyl]-N-thiazol-2-yl-propionamide (37 mg, 19.3%) as a white solid: mp 164-167° C.; EI-HRMS m/e calcd for C22H27N3OS (M+) 381.1874, found 381.1879.

Workup

  1. washThis solution was washed with water (1×10 mL)
  2. extractionThe aqueous layers were back extracted with methylene chloride (1×10 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a1423846a2984dcd8ea9da155f7ebebc
Source dataset
uspto-grants-2002_05
Patent number
US06388071B2

Reaction notes

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