C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH:20]([C:27]1[C:32]([Br:33])=[CH:31][N:30]=[C:29]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([OH:41])=[CH:37][CH:36]=2)[N:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.O[CH2:43][CH2:44][CH2:45][N:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1.N(C(OCC)=O)=NC(OCC)=O.Cl>C(Cl)Cl>[NH:20]([C:27]1[C:32]([Br:33])=[CH:31][N:30]=[C:29]([NH:34][C:35]2[CH:36]=[CH:37][C:38]([O:41][CH2:43][CH2:44][CH2:45][N:46]3[CH2:51][CH2:50][O:49][CH2:48][CH2:47]3)=[CH:39][CH:40]=2)[N:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1Triphenylphosphine (400 mg, 1.5 mmol) was added to a stirred solution of 4-anilino-5-bromo-2-(4-hydroxyanilino)pyrimidine (Method 4, 178 mg, 0.5 mmol) in DCM (40 ml) and the solution was stirred for 30 minutes. A solution of 4-(3-hydroxypropyl)morpholine (80 mg, 1.5 mmol) in DCM (2 ml) was added and the solution was stirred for 2 minutes. Diethyl azodicarboxylate (0.25 ml, 1.5 mmol) was added dropwise and the mixture was stirred for 20 hours. Volatile material was removed by evaporation and the residue was dissolved into ethyl acetate (100 ml). The solution was washed with water (2×50 ml) and then extracted with 2M hydrochloric acid (2×30 ml). The combined acidic extracts were washed with ethyl acetate (2×50 ml) and then basified by addition of 0.88 ammonia solution. The basified solution was extracted with ethyl acetate (2×50 ml) and the extracts were washed with water (2×50 ml) and saturated sodium chloride (2×50 ml) and dried. Volatile material was removed by evaporation and the residue was loaded on a Varian Mega Bond Elut column. Elution with 0-10% methanol in ethyl acetate and evaporation of the appropriate fractions gave an oil, which was treated with methanolic hydrogen chloride. Volatile material was removed by evaporation and the residue was recrystallized from a mixture of methanol and ether to give the product as a dihydrochloride salt (28 mg). NMR: 2.2 (m, 2H), 3.1 (m, 2H), 3.2 (m, 2H), 3.4 (d, 2H), 3.8-4.1 (m, 6H), 6.8 (d, 2H), 7.2-7.3 (t, 1H), 7.3-7.5 (m, 4H), 7.6 (d, 2H), 8.4 (s, 1H), 9.5 (br s, 1H), 10.1 (br s, 1H), 11.3 (br s, 1H); MS (MH+): 484, 486.
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