Dimethylacetamide → Carbonic acid 1-(5-{(R)-(4-{amino[benzoylimino]methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]-triazol-3-yloxy)propyl ester cyclohexyl ester

HRID 2089654Notes

Reaction equation

HRID 2089654 reaction equation
[NH2:1][C:2](=[N:36][C:37](=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C@H:10]([C:23]2[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH2:32][CH2:33][OH:34])[C:24]=2[F:35])[C:11]2[NH:15][C:14](=[O:16])[N:13]([C:17]3[N:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[N:12]=2)=[CH:5][CH:4]=1.CC(N(C)C)=O.[CH:51]1([O:57][C:58](=[O:64])[O:59][CH:60](Cl)[CH2:61][CH3:62])[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]1.C(=O)([O-])O.[K+]>O.C(OCC)(=O)C>[CH:51]1([O:57][C:58](=[O:64])[O:59][CH:60]([O:16][C:14]2[N:13]([C:17]3[N:18]=[CH:19][CH:20]=[CH:21][N:22]=3)[N:12]=[C:11]([C@H:10]([NH:9][C:6]3[CH:7]=[CH:8][C:3]([C:2]([NH2:1])=[N:36][C:37](=[O:44])[C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)=[CH:4][CH:5]=3)[C:23]3[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH2:32][CH2:33][OH:34])[C:24]=3[F:35])[N:15]=2)[CH2:61][CH3:62])[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]1

Participants

7

Reactant 4

HCID 31374DimethylacetamideHCID 516893Potassium BicarbonateHCID 67378388Carbonic acid 1-chloropropyl ester cyclohexyl esterHCID 136334027N-[1-amino-1-(4-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}phenyl)methylidene]benzamide

Product 1

HCID 54670297Carbonic acid 1-(5-{(R)-(4-{amino[benzoylimino]methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]-triazol-3-yloxy)propyl ester cyclohexyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of N-[1-amino-1-(4-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}phenyl)methylidene]benzamide (Example 12b, 200 mg) and DMA (2 mL), carbonic acid 1-chloropropyl ester cyclohexyl ester [CAS No. 108098-53-9] (300 mg) and potassium hydrogen carbonate (100 mg) were added, and the resulting mixture was stirred at 55° C. for 36 hours. The resulting mixture was poured into ethyl acetate and water. After shaking the mixture, the organic layer was collected, sequentially washed twice with water and with saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The resulting mixture was filtered, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was crudely purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate) to obtain a crudely purified product (120 mg).

Workup

  1. stirringAfter shaking the mixture
  2. customthe organic layer was collected
  3. washsequentially washed twice with water and with saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThe resulting mixture was filtered
  6. customthe filtrate obtained
  7. concentrationwas concentrated under reduced pressure
  8. customThe residue obtained
  9. customwas crudely purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate)

Sources & evidence

ORD record
ord-37d0c4df49b64ec28fc88e17a849f233
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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