Dimethylformamide → 5-[1-[4-(1-Acetyl-piperidin-4-yloxy)-quinolin-6-yl]-meth-(z)-ylidene]-2-amino-thiazol-4-one

HRID 853034Notes

Reaction equation

[NH2:1][C:2]1[S:3]/[C:4](=[CH:8]\[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[CH:14][CH:13]=[C:12]3[O:19][CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)/[C:5](=[O:7])[N:6]=1.[CH:26]([N:29]([CH:32]([CH3:34])C)[CH2:30][CH3:31])([CH3:28])C.[C:35](Cl)(=[O:37])[CH3:36].CN(C)C=[O:42]>ClCCl>[C:35]([N:23]1[CH2:22][CH2:21][CH:20]([O:19][C:12]2[C:11]3[C:16](=[CH:17][CH:18]=[C:9](/[CH:8]=[C:4]4/[C:5](=[O:7])[N:6]=[C:2]([NH2:1])[S:3]/4)[CH:10]=3)[N:15]=[CH:14][CH:13]=2)[CH2:25][CH2:24]1)(=[O:37])[CH3:36].[C:32]([N:29]1[CH2:26][CH2:28][CH:20]([O:19][C:12]2[C:11]3[C:16](=[CH:17][CH:18]=[C:9](/[CH:8]=[C:4]4/[C:5](=[O:7])[N:6]=[C:2]([NH:1][C:35](=[O:37])[CH3:36])[S:3]/4)[CH:10]=3)[N:15]=[CH:14][CH:13]=2)[CH2:31][CH2:30]1)(=[O:42])[CH3:34]

Participants

Conditions

Temperature: 0 °C

Procedure

The suspension of 2-amino-5-[1-[4-(piperidin-4-yloxy)-quinolin-6-yl]-meth-(Z)-ylidene]-thiazol-4-one (223 mg, 0.63 mmol, example 48) and diisopropylethyl amine(1.4 ml, 7.9 mmol) in anhydrous dichloromethane and dimethyl formamide (1:1, 8 ml) was cooled to 0° C., followed by slow addition of acetyl chloride (54 mg, 0.69 mmol) in dichloromethane (0.5 ml). The resulting solution was then warmed up to room temperature for 1 hr. Both 5-[1-[4-(1-Acetyl-piperidin-4-yloxy)-quinolin-6-yl]-meth-(Z)-ylidene]-2-amino-thiazol-4-one and N-{5-[1-[4-(1-acetyl-piperidin-4-yloxy)-quinolin-6-yl]-meth-(Z)-ylidene]-4-oxo-4,5-dihydro-thiazol-2-yl}-acetamide were obtained. Then the solution was treated with sodium hydroxide (aq., 1N, 7 ml) at room temperature for overnight. After removing the solvents, a yellow solid was collected. HPLC (YMC C18, 2%-60% CH3CN/H2O in 20 min, float rate 20 ml/min) afforded 5-[1-[4-(1-acetyl-piperidin-4-yloxy)-quinolin-6-yl]-meth-(Z)-ylidene]-2-amino-thiazol-4-one (76 mg, 30%) as light yellow solid. LC-MS m/e 397 (MH+).

Workup

temperatureThe resulting solution was then warmed up to room temperature for 1 hr

Sources & evidence

ORD record: ord-e5c6b91979b74bfb8f85b2b46c46eb9e
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07253285B2

Reaction notes

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