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

HRID 347736Notes

Reaction equation

HRID 347736 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][N:3]=1.Cl.[CH3:18][N:19]([CH2:21][CH:22]([OH:32])[CH2:23][O:24][C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=1)[CH3:20].CO.N>C(O)CCC>[CH3:20][N:19]([CH2:21][CH:22]([OH:32])[CH2:23][O:24][C:25]1[CH:26]=[CH:27][C:28]([NH:29][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=3[F:16])[CH:5]=[CH:4][N:3]=2)=[CH:30][CH:31]=1)[CH3:18]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 887MethanolHCID 179811362-Chloro-4-(2,4-difluoroanilino)pyrimidineHCID 227319204-[2-hydroxy-3-(N,N-dimethylamino)propoxy]aniline hydrochloride

Product 1

HCID 210837252-{4-[3-(N,N-Dimethyl)amino-2-hydroxypropoxy]anilino}-4-(2,4-difluoroanilino)pyrimidineYield 41.5%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

2-Chloro-4-(2,4-difluoroanilino)pyrimidine (Reference Example A-2; 174 mg, 0.72 mmol) was dissolved in n-butanol (2 ml) and 4-[3-(N,N-dimethyl)amino-2-hydroxypropoxy]aniline hydrochloride (Reference Example D-1; 198 mg, 0.72 mmol) was added. The resulting suspension was treated with methanol until all the solid dissolved. The reaction mixture was heated at 100° C. for 12 hours and allowed to cool to ambient temperature. The reaction mixture was then basified to pH 9–10 using methanolic ammonia and evaporated onto silica (5 ml). The residue was purified by column chromatography eluting with methanol (15%): DCM:aqueous ammonia(1%). The resulting gum was recrystallized from acetonitrile to give the title product as a solid (124 mg, 41%). NMR (300 MHz): 2.18 (s, 6H), 2.34 (m, 2H), 3.78 (m, 1H), 3.88 (m, 2H), 4.75 (brd, 1H), 6.18 (d, 1H), 6.75 (d, 2H), 7.03 (t, 1H), 7.32 (t, 1H), 7.48 (d, 2H), 7.88 (dd, 1H), 7.95 (d, 1H), 8.88 (s, 1H), 8.95(s, 1H); m/z: (ES+) 416.4 (MH+).

Workup

  1. dissolutiondissolved
  2. temperatureto cool to ambient temperature
  3. customevaporated onto silica (5 ml)
  4. customThe residue was purified by column chromatography
  5. washeluting with methanol (15%)
  6. customThe resulting gum was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-b755efa91aaf4546addb480a8da43398
Source dataset
uspto-grants-2007_02
Patent number
US07176212B2

Reaction notes

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