Isopropanol → 2-benzyl-4-(2-propoxy)-5-[4-(methylthio)pentyl]-3(2H)-pyridazinone

HRID 381879Notes

Reaction equation

HRID 381879 reaction equation
C(N1C(=O)[C:12](Cl)=[C:11]([O:16]C)[CH:10]=N1)C1C=CC=CC=1.CSC1C=CC(B(O)O)=CC=1.[CH2:29]([N:36]1[C:41](=[O:42])[C:40](Cl)=[C:39]([C:44]2[CH:49]=[CH:48][C:47]([S:50][CH3:51])=[CH:46]C=2)[CH:38]=[N:37]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.CC(O)C.CC(C)([O-])C.[K+]>>[CH2:29]([N:36]1[C:41](=[O:42])[C:40]([O:16][CH:11]([CH3:12])[CH3:10])=[C:39]([CH2:44][CH2:49][CH2:48][CH:47]([S:50][CH3:51])[CH3:46])[CH:38]=[N:37]1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

6

Reactant 5

HCID 3776IsopropanolHCID 7370152-Benzyl-4-chloro-5-methoxypyridazin-3(2h)-oneHCID 27339594-(Methylthio)phenylboronic acidHCID 219339762-benzyl-4-chloro-5-[4-(methylthio)phenyl]-3(2H)-pyridazinoneHCID 23665647Potassium tert-butoxide

Product 1

HCID 537141662-benzyl-4-(2-propoxy)-5-[4-(methylthio)pentyl]-3(2H)-pyridazinone

Procedure

2-Benzyl-4-chloro-5-methoxy-3(2H)-pyridazinone (J. Het. Chem., 1996, 33, 1579-1582) was converted to the 5-hydroxy-analog according to the method of Example 7 and then to the 5-trifluoromethylsulfonyloxy-analog following the method of Example 8. Subsequent coupling to 4-(methylthio)phenylboronic acid according to the method of Example 9 provided 2-benzyl-4-chloro-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone. This 4-chloro-intermediate thus prepared was treated with 2-propanol (20 mL, 261 mmol) and potassium t-butoxide (110 mg, 0.98 mmol) at reflux for 45 minutes furnished 2-benzyl-4-(2-propoxy)-5-[4-(methylthio)pentyl]-3(2H)-pyridazinone. This methyl sulfide was oxidized according to the method of Example 10 to provide the title compound (yield: 180 mg, 80%). mp 109-111° C. 1H NMR (300 MHz, CDCl3) δ 1.18 (d, J=6 Hz, 6H), 3.12 (s, 3H), 5.36 (s, 2H), 5.49 (h, J=6 Hz, 1H), 7.35 (m, 3H), 7.47 (dd, J=9 Hz, 3 Hz, 2H), 7.74 (d, J=9 Hz, 2H), 7.79 (s, 1H), 8.03 (d, J=9 Hz, 2H). MS (DCI/NH3) m/z 399 (M+H)+. Anal. calc. for C21H22N2O4S: C, 63.29; H, 5.56; N, 7.03. Found: C, 63.17; H, 5.57; N, 6.95.

Workup

  1. temperatureat reflux for 45 minutes

Sources & evidence

ORD record
ord-f825715508374c94b777641cd3d04bf0
Source dataset
uspto-grants-2001_10
Patent number
US06307047B1

Reaction notes

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