4-chloro-N-phenylpyrimidin-2-amine → 2-Anilino-4-{4-[3-(N,N-dimethyl)amino-2-hydroxypropoxy]anilino}pyrimidine

HRID 347748Notes

Reaction equation

[NH:1]([C:8]1[N:13]=[C:12](Cl)[CH:11]=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:16][N:17]([CH2:19][CH:20]([OH:30])[CH2:21][O:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1)[CH3:18]>C(O)CCC.CO>[NH:1]([C:8]1[N:13]=[C:12]([NH:27][C:26]2[CH:28]=[CH:29][C:23]([O:22][CH2:21][CH:20]([OH:30])[CH2:19][N:17]([CH3:16])[CH3:18])=[CH:24][CH:25]=2)[CH:11]=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

2-Anilino-4-chloropyrimidine (145 mg, 0.71 mmol) was dissolved in n-butanol (20 ml). To this solution was added a hot solution of 4-[3-(N,N-dimethyl)amino-2-hydroxy-propoxy]aniline hydrochloride (Reference Example D-1; 178 mg, 0.63 mmol) in methanol (2 ml). The reaction mixture was heated at 80° C. for 18 hours, allowed to cool to ambient temperature and then evaporated onto silica (3 ml). The residue was purified by column chromatography eluting with 0–8% 2.0M methanolic ammonia solution in DCM to give the title product as a colourless solid (157 mg, 65%). NMR (300 MHz): 2.18 (s, 6H), 2.33 (m, 2H), 3.83 (m, 3H), 4.77 (d, 1H), 6.11 (d, 1H), 6.86 (m, 3H), 7.19 (m, 2H), 7.51 (d, 2H), 7.69 (d, 2H), 7.96 (d, 1H), 9.01 (s, 1H), 9.08 (s, 1H); m/z: (ES+) 380.4 (MH+).

Workup

temperatureto cool to ambient temperature
customevaporated onto silica (3 ml)
customThe residue was purified by column chromatography
washeluting with 0–8% 2.0M methanolic ammonia solution in DCM

Sources & evidence

ORD record: ord-ac223a5d317d4cb39a5d0b455ae18234
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07176212B2

Reaction notes

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