Water → Phthalazine

Lithium hexamethyldisilazide (1.0M solution in hexane) (0.22 ml, 1.10 mmol) was added to stirred solution of 3-hydroxymethyl-1-methyl-1,2,4-triazole (90 mg, 0.79 mmol) prepared using the conditions of Itoh and Okongi, EP-A-421210) in N,N-dimethylformamide (10 ml) at −10° C. under nitrogen, and the mixture stirred for 0.25 h. After this time, Intermediate 6 (100 mg, 0.53 mmol) was added and the mixture stirred at −10° C. for 0.5 h and then room temperature overnight. Water was added to the reaction mixture and the resulting precipitate filtered off and recrystallised from dichloromethane/ethyl acetate to give the title-phthalazine (55 mg, 27%), mp 221-223° C.; 1H NMR (360 MHz, CDCl3) δ 1.54 (3H, t, J=10.2 Hz; CH3), 3.96 (3H, s, CH3), 4.47 (2H, q, J=10.2 Hz, CH2), 5.71 (2H, s, CH2), 6.26 (1H, s, Ar—H), 7.79 (1H, m, Ar—H), 7.94 (1H, m, Ar—H), 8.08 (1H, s, Ar—H), 8.25 (1H, d, J=11.0 Hz, Ar—H), 8.70 (1H, d, J=8.1 Hz, Ar—H); MS (ES+) m/e 393 [MH]+; Anal. Found. C, 54.87; H, 3.91; N, 28.27; C18H16N8O3 requires C, 55.09; H, 4.11; N, 28.55%.

1. customprepared
2. customat −10° C.
3. stirringthe mixture stirred at −10° C. for 0.5 h
4. customroom temperature overnight
5. filtrationthe resulting precipitate filtered off
6. customrecrystallised from dichloromethane/ethyl acetate

ORD-Eintrag

ord-c28531e728fd4cc7b1aca5eb1343375e

Quelldatensatz

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06310203B1