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

HRID 1247643Notes

Reaction equation

HRID 1247643 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][O:28]C(=O)C)[CH:23]=[CH:24][CH:25]=4)[N:17]=[CH:18][C:13]=3[CH:12]([CH3:32])[N:11]([C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)[C:10]2=[O:41])[CH:6]=[CH:7][CH:8]=1)#[N:2].C(=O)([O-])[O-].[K+].[K+]>CO.O>[OH:28][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:41])[N:11]([C:33]4[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=4)[CH:12]([CH3:32])[C:13]3=[CH:18][N:17]=2)[CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 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

Product 1

HCID 9870839(+/-)-3-[7-[3-(2-hydroxy-ethyl)-phenylamino]-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

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 (10 g; 1.81 mmol) (from Example 3c supra) was dissolved in a mixture of methanol (17 mL) and water (7 mL) and treated with potassium carbonate (1.00 g; 7.26 mmol) at room temperature for 19 hours. The reaction mixture was partitioned between ethyl acetate and water-brine mixture. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude material was purified by flash chromatography (Biotage 40M; ethyl acetate) to give (±)-3-[7-[3-(2-hydroxy-ethyl)-phenylamino]-3-(4-methoxy-phenyl)-4-methyl-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl]-benzonitrile. (Yield 0.67 g; 72.9%). A small amount of additional material bumped over into the solvent trap during concentration. This material was recovered and crystallized from ethyl acetate. (Yield 0.09 g; 9.9%). Melting Point: 195–200° C. HR-MS(ES+) m/z Calculated for C29H26N6O3 ([M+H]+): 507.2139. Found: 507.2145. HR-MS(ES+) m/z Calculated for C29H26N6O3 ([M+Na]+): 529.9158. Found: 529.1963.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water-brine mixture
  2. washThe organic phase was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash chromatography (Biotage 40M; ethyl acetate)

Sources & evidence

ORD record
ord-7ba85dcfc319497b8a49e156595312e8
Source dataset
uspto-grants-2006_10
Patent number
US07129351B2

Reaction notes

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