2-Aminothiazole → 3-cyclopentyl-2-(1-oxo-1H-phthalazin-2-yl)-N-thiazol-2-yl-propionamide

HRID 2381502Notes

Reaction equation

HRID 2381502 reaction equation
[CH:1]1([CH2:6][CH:7]([N:11]2[N:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]2=[O:21])[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.[S:51]1[CH:55]=[CH:54][N:53]=[C:52]1[NH2:56]>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([N:11]2[N:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]2=[O:21])[C:8]([NH:56][C:52]2[S:51][CH:55]=[CH:54][N:53]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 66891968HCID 66891968, compound

Product 1

HCID 579191973-cyclopentyl-2-(1-oxo-1H-phthalazin-2-yl)-N-thiazol-2-yl-propionamideYield 61.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(1-oxo-1H-phthalazin-2-yl)-propionic acid (0.31 g, 1.09 mmol) in methylene chloride (6.10 mL, 0.18M) at 25° C. was treated with N,N-diisopropylethylamine (0.57 mL, 3.29 mmol) and N,N,N′,N′-tetramethyl-O—(N-succinimidyl)uronium tetrafluoroborate (0.39 g, 1.31 mmol). The resulting solution was stirred at 25° C. for 2 h. After this time, the reaction was treated with thiazol-2-ylamine (143 mg, 1.42 mmol). The resulting solution was stirred at 25° C. overnight. After this time, the reaction was partitioned between water (100 mL) and methylene chloride (3×75 mL). The combined organics were washed with water (1×100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (ISCO, 40 g, 50% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-(1-oxo-1H-phthalazin-2-yl)-N-thiazol-2-yl-propionamide as a white solid (247.7 mg, 61%); ES+-HRMS m/e calcd for C19H20N4O2S [M+H+] 369.1380 found 369.1378. 1H-NMR (300 MHz, DMSO-d6) δ ppm 0.99-1.17 (m, 1H), 1.20-1.80 (m, 8H), 2.04-2.18 (m, 1H), 2.23-2.36 (m, 1H), 5.73 (dd, J=10.4, 4.4 Hz, 1H), 7.22 (d, J=3.4 Hz, 1H), 7.47 (d, J=3.4 Hz, 1H), 7.83-7.93 (m, 1H), 7.94-8.02 (m, 2H), 8.26 (d, J=7.8 Hz, 1H), 8.52 (s, 1H), 12.46 (s, 1H).

Workup

  1. stirringThe resulting solution was stirred at 25° C. overnight
  2. customAfter this time, the reaction was partitioned between water (100 mL) and methylene chloride (3×75 mL)
  3. washThe combined organics were washed with water (1×100 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-af0407780c70408594ced53069d0a147
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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