Phosgene → [5-(3-Chloro-benzyl)-4-methyl-thiazol-2-yl]-(4-[1,2,4]triazol-1-yl-phenyl)-amine

HRID 604870

Reaction equation

[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13]([NH2:15])=[S:14])=[CH:8][CH:7]=2)[CH:5]=[N:4][CH:3]=[N:2]1.Cl[CH:17]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=1)[C:18](=O)[CH3:19].C(N(CC)C(C)C)(C)C.ClC(Cl)=O>C(O)C>[Cl:28][C:24]1[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=1)[CH2:21][C:17]1[S:14][C:13]([NH:12][C:9]2[CH:8]=[CH:7][C:6]([N:1]3[CH:5]=[N:4][CH:3]=[N:2]3)=[CH:11][CH:10]=2)=[N:15][C:18]=1[CH3:19]

Participants

Conditions

Temperature: 170 °C

Procedure

A suspension of 55 mg (0.25 mmol) 4-(1,2,4-triazol-1-yl)phenylthiourea, of 60 mg (0.28 mmol) 3-chloro-4-(3-chlorophenyl)-2-butanone and of 65 mg (0.5 mmol) N,N-diisopropyl ethyl amine in ethanol (2.5 ml) was refluxed over night. The same amount of chloro ketone was added and the reaction was heated to reflux over night. Again 1.1 equivalent of chloro ketone was added and the reaction was heated for 10 minutes in a microwave oven to 170° C. The solvent was evaporated and the residue was purified on silica gel with methylene chloride/methanol 19/1 yielding 27 mg (28%) [5-(3-chloro-benzyl)-4-methyl-thiazol-2-yl]-(4-[1,2,4]triazol-1-yl-phenyl)-amine as a yellow solid. MS ISP (m/e): 382.1 (100) (M+H)+. 1H NMR (CDCl3, 250 MHz): δ (ppm)=8.48 (s, 1H), 8.09 (s, 1H), 7.60 (d, 2H), 7.46 (d, 2H), 7.25-7.18 (m, 3H), 7.09 (d, 1H), 3.96 (s, 2H), 2.29 (s, 3H).

Workup

temperaturethe reaction was heated
temperatureto reflux over night
customThe solvent was evaporated
customthe residue was purified on silica gel with methylene chloride/methanol 19/1 yielding 27 mg (28%) [5-(3-chloro-benzyl)-4-methyl-thiazol-2-yl]-(4-[1,2,4]triazol-1-yl-phenyl)-amine as a yellow solid

Sources & evidence

ORD record: ord-a3be7135f3944c2087df2195ee7e0bd6
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07910740B2

Linked notes

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