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

HRID 1247642Notes

Reaction equation

HRID 1247642 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([C:22]3[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=3)[C:25]#[N:26])[C:9](=[O:21])[N:10]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[CH:11]([CH3:12])[C:5]2=[CH:4][N:3]=1.[NH2:30][C:31]1[CH:32]=[C:33]([CH2:37][CH2:38][O:39][C:40](=[O:42])[CH3:41])[CH:34]=[CH:35][CH:36]=1>>[C:25]([C:24]1[CH:23]=[C:22]([N:8]2[C:6]3[N:7]=[C:2]([NH:30][C:31]4[CH:32]=[C:33]([CH2:37][CH2:38][O:39][C:40](=[O:42])[CH3:41])[CH:34]=[CH:35][CH:36]=4)[N:3]=[CH:4][C:5]=3[CH:11]([CH3:12])[N:10]([C:13]3[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=3)[C:9]2=[O:21])[CH:29]=[CH:28][CH:27]=1)#[N:26]

Participants

3

Reactant 2

HCID 10363933(+/-)-3-[7-chloro-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrileHCID 587222382-(3-Aminophenyl)ethyl acetate

Product 1

HCID 10256942(+/-)-Acetic 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

Conditions

Temperature
110 °C

Procedure

A mixture of (±)-3-[7-chloro-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile (1.00 g; 2.42 mmol) (from Example 2 supra) and acetic acid 2-(3-amino-phenyl)-ethyl ester (2.03 g; 11.3 mmol) (from Example 3b supra) was heated in an oil bath at 110° C. for 1.5 hours. Upon cooling, the mixture was triturated with hexanes containing a small volume of ethyl acetate. The supernatant was decanted away and the residue was purified, in two runs, by flash chromatography (Biotage 40M; 50:50 to 70:30 ethyl acetate-hexanes gradient). The purified material was crystallized from ethyl acetate-hexanes to give (±)-acetic 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 as a white solid. (1.03 g; 77.5%). Melting Point: 170–172° C.

Workup

  1. temperatureUpon cooling
  2. customthe mixture was triturated with hexanes containing a small volume of ethyl acetate
  3. customThe supernatant was decanted away
  4. customthe residue was purified, in two runs, by flash chromatography (Biotage 40M; 50:50 to 70:30 ethyl acetate-hexanes gradient)
  5. customThe purified material was crystallized from ethyl acetate-hexanes

Sources & evidence

ORD record
ord-79ba91c994e840b4b74cfcd7356baee8
Source dataset
uspto-grants-2006_10
Patent number
US07129351B2

Reaction notes

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