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

HRID 347740Notes

Reaction equation

HRID 347740 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([CH2:15][C:16](=[O:18])[NH2:17])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.Cl.Cl.[CH3:21][N:22]([CH2:24][CH:25]([OH:35])[CH2:26][O:27][C:28]1[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][CH:29]=1)[CH3:23].N>CN1C(=O)CCC1>[CH3:23][N:22]([CH2:24][CH:25]([OH:35])[CH2:26][O:27][C:28]1[CH:29]=[CH:30][C:31]([NH:32][C:2]2[N:7]=[C:6]([N:8]([CH2:15][C:16](=[O:18])[NH2:17])[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:5]=[CH:4][N:3]=2)=[CH:33][CH:34]=1)[CH3:21]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 180091401-(4-Aminophenoxy)-3-(dimethylamino)propan-2-ol;dihydrochlorideHCID 210837442-Chloro-4-(N-(carbamoylmethyl)anilino)pyrimidine

Product 1

HCID 210837312-{4-[3-(N,N-Dimethyl)amino-2-hydroxypropoxy]anilino}-4-(N-(carbamoylmethyl)anilino)pyrimidine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

2-Chloro-4-(N-(carbamoylmethyl)anilino)pyrimidine (prepared by analogy to Method A and the corresponding Reference Examples A-1–A-10) (390 mg, 1.49 mmol) was dissolved in NMP (3 ml) and 4-[3-(N,N-dimethyl)amino-2-hydroxypropoxy]aniline dihydrochloride (Reference Example D-1; 378 mg, 1.34 mmol) was added. The resulting suspension was heated at 120° C. which caused the solid to dissolve. The reaction mixture was heated at 120° 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 then evaporated onto silica (5 ml). The residue was purified by column chromatography eluting with methanol (15%):DCM:aqueous ammonia (1%). The resulting gum was re-evaporated from EtOAc three times to give the title product as a foam (184 mg). NMR: (300 MHz) 2.31 (s, 6H), 2.49 (m, 2H), 3.8 (m, 1H), 3.92 (m, 2H), 4.42 (s, 2H), 5.68 (d, 1H), 6.79 (d, 2H), 7.4) (m, 5H), 7.58 (d, 2H), 7.82 (d, 1H), 8.93 (s, 1H); m/z: (ES+) 437.5 (MH+).

Workup

  1. dissolutionto dissolve
  2. temperatureThe reaction mixture was heated at 120° C. for 12 hours
  3. temperatureto cool to ambient temperature
  4. customevaporated onto silica (5 ml)
  5. customThe residue was purified by column chromatography
  6. washeluting with methanol (15%)
  7. customThe resulting gum was re-evaporated from EtOAc three times

Sources & evidence

ORD record
ord-d63f16261b1941a1a23d120beeb1efae
Source dataset
uspto-grants-2007_02
Patent number
US07176212B2

Reaction notes

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