Acetic Acid → 4-({[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)benzonitrile

HRID 2089685Notes

Reaction equation

HRID 2089685 reaction equation
COC(=O)[O:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[C:10]([C:16](=[N:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]#[N:37])=[CH:32][CH:31]=2)[C:17]2[NH:21][C:20](=[O:22])[N:19]([C:23]3[N:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[N:18]=2)[C:9]=1[F:38].C([BH3-])#N.[Na+].C(O)(=O)C.[OH-].[Na+]>O.O1CCCC1.CO>[F:38][C:9]1[C:8]([O:7][CH2:6][CH2:5][OH:4])=[CH:13][C:12]([O:14][CH3:15])=[CH:11][C:10]=1[CH:16]([NH:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]#[N:37])=[CH:34][CH:35]=1)[C:17]1[NH:21][C:20](=[O:22])[N:19]([C:23]2[N:24]=[CH:25][CH:26]=[CH:27][N:28]=2)[N:18]=1

Participants

8

Reactant 4

HCID 176Acetic Acid2×HCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 136334031Carbonic acid 2-{3-[(4-cyanophenylimino)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy}ethyl ester methyl ester

Product 1

HCID 1359820764-({[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)benzonitrileYield 93.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
15 °C

Procedure

A suspension of carbonic acid 2-{3-[(4-cyanophenylimino)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy}ethyl ester methyl ester (25.0 g, 47.1 mmol) and methanol (90 mL) was cooled to 15° C. Sodium cyanoborohydride (5.45 g, 87 mmol) was added thereto, and was rinsed with methanol (10 mL). Acetic acid (21.5 mL, 375 mmol) was added dropwise thereto, and the resulting mixture was stirred at room temperature for 28 hours. The mixture was cooled in an ice-water bath, and tetrahydrofuran (100 mL) and a 5 N aqueous sodium hydroxide solution (113 mL, 565 mmol) were added thereto. After stirring the resulting mixture for 18 hours, the mixture was cooled to 15° C. or below, and acetic acid (81 mL, 1.410 mol) was added thereto. To the solution obtained, a seed crystal (5.0 mg) of the captioned compound was added at room temperature, and water (250 mL) was added dropwise to the resulting mixture, after which the resulting mixture was stirred at 4° C. for 21.5 hours. The suspension obtained was filtered and was washed with 25% aqueous methanol (100 mL) and dried at 40° C. under reduced pressure to obtain the captioned compound (21.1 g) as a white solid.

Workup

  1. washwas rinsed with methanol (10 mL)
  2. temperatureThe mixture was cooled in an ice-water bath
  3. stirringAfter stirring the resulting mixture for 18 hours
  4. temperaturethe mixture was cooled to 15° C. or below
  5. customTo the solution obtained
  6. stirringafter which the resulting mixture was stirred at 4° C. for 21.5 hours
  7. customThe suspension obtained
  8. filtrationwas filtered
  9. washwas washed with 25% aqueous methanol (100 mL)
  10. customdried at 40° C. under reduced pressure

Sources & evidence

ORD record
ord-e9fef781901d462c8c180cccbb6bfc5a
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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