2-Chloro-4-(N-(2-phenylethyl)anilino)pyrimidine → 2-{4-[3-(N,N-Dimethyl)amino-2-hydroxypropoxy]anilino}-4-(N-(2-phenylethyl)anilino)pyrimidine

HRID 347751Notes

Reaction equation

HRID 347751 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.Cl.[CH3:24][N:25]([CH2:27][CH:28]([OH:38])[CH2:29][O:30][C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=1)[CH3:26]>CN1C(=O)CCC1>[CH3:26][N:25]([CH2:27][CH:28]([OH:38])[CH2:29][O:30][C:31]1[CH:32]=[CH:33][C:34]([NH:35][C:2]2[N:7]=[C:6]([N:8]([CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:5]=[CH:4][N:3]=2)=[CH:36][CH:37]=1)[CH3:24]

Participants

4

Reactant 2

HCID 210837402-Chloro-4-(N-(2-phenylethyl)anilino)pyrimidineHCID 227319204-[2-hydroxy-3-(N,N-dimethylamino)propoxy]aniline hydrochloride

Product 1

HCID 210837282-{4-[3-(N,N-Dimethyl)amino-2-hydroxypropoxy]anilino}-4-(N-(2-phenylethyl)anilino)pyrimidineYield 36%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

2-Chloro-4-(N-(2-phenylethyl)anilino)pyrimidine (Reference Example E-3; 270 mg, 0.87 mmol) was dissolved in NMP (2 ml), 4-[3-(N,N-dimethyl)amino-2-hydroxypropoxy]aniline hydrochloride (Reference Example D-1; 222 mg, 0.90 mmol) was added and the mixture heated at 120° C. for 12 hours. The solvent was evaporated, the residue was resolubilized in methanol/ammonia 6M and evaporated again to dryness. The resulting solid was purified by flash chromatography using increasingly polar solvent mixtures starting with DCM and ending with DCM/methanol with 10% ammonia (87.5/12.5). Evaporation of the solvent gave a foam which was triturated in ether to give the title product as a white solid (150 mg, 36%). NMR: (400 MHz, 353K) 2.30 (s, 6H), 2.50 (m, 2H), 2.90 (m, 2H), 3.80 (m, 1H), 3.85 (m, 1H), 3.95 (br s, 1H), 4.10 (m, 2H), 5.00 (br s, 1H), 5.50 (d, 1H), 6.70 (d, 2H), 7.15 (m, 3H), 7.25(m, 4H), 7.35 (t, 1H), 7.50 (t, 2H), 7.60 (d, 2H), 7.80 (d, 1H), 8.85 (s, 1H), M.S.: (ES+) 484 (MH+).

Workup

  1. customThe solvent was evaporated
  2. customevaporated again to dryness
  3. customThe resulting solid was purified by flash chromatography
  4. temperatureusing increasingly polar solvent mixtures
  5. customEvaporation of the solvent
  6. customgave a foam which
  7. customwas triturated in ether

Sources & evidence

ORD record
ord-c3eeb2002ddf48d3b852e626ee2eed59
Source dataset
uspto-grants-2007_02
Patent number
US07176212B2

Reaction notes

Loading…