Diethylamine → (+/-)-3-[7-[3-(2-diethylamino-ethyl)-phenylamino]-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile

HRID 1247645Notes

Reaction equation

HRID 1247645 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([N:9]2[C:14]3[N:15]=[C:16]([NH:19][C:20]4[CH:21]=[C:22]([CH2:26][CH2:27]OS(C)(=O)=O)[CH:23]=[CH:24][CH:25]=4)[N:17]=[CH:18][C:13]=3[CH:12]([CH3:33])[N:11]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)[C:10]2=[O:42])[CH:6]=[CH:7][CH:8]=1)#[N:2].[CH2:43]([NH:45][CH2:46][CH3:47])[CH3:44]>>[CH2:43]([N:45]([CH2:46][CH3:47])[CH2:27][CH2:26][C:22]1[CH:21]=[C:20]([NH:19][C:16]2[N:15]=[C:14]3[N:9]([C:5]4[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=4)[C:1]#[N:2])[C:10](=[O:42])[N:11]([C:34]4[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=4)[CH:12]([CH3:33])[C:13]3=[CH:18][N:17]=2)[CH:25]=[CH:24][CH:23]=1)[CH3:44]

Participants

3

Reactant 2

HCID 8021DiethylamineHCID 10325979(+/-)-Methanesulfonic acid (2-{3-[8-(3-cyano-phenyl)-6-(4-methoxy-phenyl)-5-methyl-7-oxo-5,6,7,8-tetrahydro-pyrimido[4,5-d]pyrimidin-2-ylamino]-phenyl}-ethyl)-ester

Product 1

HCID 10076529(+/-)-3-[7-[3-(2-diethylamino-ethyl)-phenylamino]-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile

Conditions

Temperature
100 °C

Procedure

A mixture of (±)-methanesulfonic acid (2-{3-[8-(3-cyano-phenyl)-6-(4-methoxy-phenyl)-5-methyl-7-oxo-5,6,7,8-tetrahydro-pyrimido[4,5-d]pyrimidin-2-ylamino]-phenyl}-ethyl)-ester (1.18 g; 2.02 mmol) (from Example 5a supra) and diethylamine (1.5 mL; 14.5 mmol) (Aldrich) in a pressure bottle and heated at 100° C. for 100 minutes. Upon cooling, the mixture was concentrated and the residue was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated. Purification by flash chromatography (Biotage 40S; 100:0 to 50:50 ethyl acetate-methanol) followed by crystallization from ethyl acetate and hexanes gave (±)-3-[7-[3-(2-diethylamino-ethyl)-phenylamino]-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile. (Yield 0.66 g; 57.9%).

Workup

  1. temperatureUpon cooling
  2. concentrationthe mixture was concentrated
  3. customthe residue was partitioned between ethyl acetate and water
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customPurification by flash chromatography (Biotage 40S; 100:0 to 50:50 ethyl acetate-methanol)
  8. customfollowed by crystallization from ethyl acetate and hexanes

Sources & evidence

ORD record
ord-d42c873a52df4c0fb5349ff2fa276fd3
Source dataset
uspto-grants-2006_10
Patent number
US07129351B2

Reaction notes

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