2-Aminothiazole → 3-cyclopentyl-2-(4-methoxy-6-oxo-6H-pyridazin-1-yl)-N-thiazol-2-yl-propionamide

HRID 2381497Notes

Reaction equation

HRID 2381497 reaction equation
[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][CH3:19])[CH:13]=[N:12]2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.C(N(CC)C(C)C)(C)C.[S:49]1[CH:53]=[CH:52][N:51]=[C:50]1[NH2:54]>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][CH3:19])[CH:13]=[N:12]2)[C:8]([NH:54][C:50]2[S:49][CH:53]=[CH:52][N:51]=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 668754403-cyclopentyl-2-(4-methoxy-6-oxo-6H-pyridazin-1-yl)-propionic acid

Product 1

HCID 579191213-cyclopentyl-2-(4-methoxy-6-oxo-6H-pyridazin-1-yl)-N-thiazol-2-yl-propionamideYield 32.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(4-methoxy-6-oxo-6H-pyridazin-1-yl)-propionic acid (100 mg, 0.37 mmol) in methylene chloride (2.08 mL, 0.18M) at 25° C. was treated with N,N,N′,N′-tetramethyl-O—(N-succinimidyl)uronium tetrafluoroborate (135.6 mg, 0.45 mmol) and N,N-diisopropylethylamine (0.196 mL, 1.12 mmol). The resulting solution was stirred at 25° C. for 2 h. After this time, the reaction was treated with thiazol-2-ylamine (49 mg, 0.48 mmol). The resulting solution was stirred at 25° C. for 1 d. After this time, the reaction was partitioned between water (75 mL) and methylene chloride (3×75 mL). The combined organics were dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (ISCO, 40 g, 1% methanol/methylene chloride) afforded 3-cyclopentyl-2-(4-methoxy-6-oxo-6H-pyridazin-1-yl)-N-thiazol-2-yl-propionamide as a white solid (41.4 mg, 32%); ES+-HRMS m/e calcd for C16H20N4O3S [M+H+] 349.1329, found 349.1328. 1H-NMR (300 MHz, DMSO-d6) δ ppm 0.98-7.78 (m, 9H), 1.95 (m, 1H), 2.27 (m, 1H), 3.82 (s, 3H), 5.54 (dd, J=4.5, J=10.6 Hz, 1H), 6.32 (d, Jm=2.7 Hz, 1H), 7.23 (d, J=3.6 Hz, 1H), 7.48 (d, J=3.6 Hz, 1H), 7.88 (d, Jm=2.7 Hz, 1H), 12.53 (s, 1H).

Workup

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

Sources & evidence

ORD record
ord-f02923bc61584c5c885ec1a1b5ca8d3e
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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