Hydrochloric Acid → N4-{4-Azido-phenyl)-6-(2-ethoxy-5-iodo-phenyl)-pyrimidine-2,4-diamine

HRID 28632Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([I:14])[CH:11]=[CH:10][C:9]=2[O:15][CH2:16][CH3:17])[N:5]=[C:4]([NH2:18])[N:3]=1.Cl.[N:20]([C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1)=[N+:21]=[N-:22].Cl.C(=O)(O)[O-].[Na+]>C(O)(C)(C)C.O1CCOCC1>[N:20]([C:23]1[CH:29]=[CH:28][C:26]([NH:27][C:2]2[CH:7]=[C:6]([C:8]3[CH:13]=[C:12]([I:14])[CH:11]=[CH:10][C:9]=3[O:15][CH2:16][CH3:17])[N:5]=[C:4]([NH2:18])[N:3]=2)=[CH:25][CH:24]=1)=[N+:21]=[N-:22]

Participants

Conditions

Temperature: 90 °C

Procedure

To a mixture of 4-chloro-6-(5-iodo-2-ethoxy-phenyl)pyrimidin-2-ylamine (7.0 mg, 0.02 mmol) and 4-azidoaniline hydrochloride (5.0 mg, 0.03 mmol) in tert-butanol (1 ml) was added a 1 M hydrogen chloride in dioxane (0.2 ml). The mixture was heated at 90° C. for 2 hours. After cooling to room temperature, the mixture was treated with 1 M aqueous sodium bicarbonate solution (1 ml) and extracted with ethyl acetate (2×1 ml). The combined extracts were concentrated under reduced pressure and the residue was purified by preparative TLC eluting with 35% ethyl acetate-hexane to provide the title compound (6 mg, 68% yield) as a light brown solid. 1H NMR (CDCl3) δ 8.20 (d, J=2.3 Hz, 1H), 7.60 (dd, J=2.3, 8.70 Hz, 1H), 7.38 (d, J=8.70 Hz, 2H), 7.04 (d, J=8.70 Hz, 2H), 6.77 (s, 1H), 6.72 (d, J=5.0 Hz, 1H), 6.63 (br s, 1H), 4.91 (br s, 2H), 4.09 (q, J=7.0 Hz, 2H), 1.38 (t, J=7.0 Hz, 3H).

Workup

temperatureAfter cooling to room temperature
extractionextracted with ethyl acetate (2×1 ml)
concentrationThe combined extracts were concentrated under reduced pressure
customthe residue was purified by preparative TLC
washeluting with 35% ethyl acetate-hexane

Sources & evidence

ORD record: ord-450765fce7e542099bb4ff8ebb34028e
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07419984B2

Reaction notes

Loading…