Acetic Anhydride → Acetic acid 2-{3-[(R)-{4-[amino(2-methylallyloxycarbonylimino)methyl]phenylamino}-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy}ethyl ester

HRID 2089691

Reaction equation

HRID 2089691 reaction equation
C[O:2][C@H:3](C1C=CC=CC=1)[C:4](O)=O.[F:13][C:14]1[C:19]([O:20][CH2:21][CH2:22][OH:23])=[CH:18][C:17]([O:24][CH3:25])=[CH:16][C:15]=1[C@@H:26]([NH:39][C:40]1[CH:48]=[CH:47][C:43]([C:44]([NH2:46])=[NH:45])=[CH:42][CH:41]=1)[C:27]1[NH:31][C:30](=[O:32])[N:29]([C:33]2[N:38]=[CH:37][CH:36]=[CH:35][N:34]=2)[N:28]=1.[N+](C1C=CC(O[C:59](=[O:65])[O:60][CH2:61][C:62]([CH3:64])=[CH2:63])=CC=1)([O-])=O.C(N(CC)CC)C.C(OC(=O)C)(=O)C>CN(C)C1C=CN=CC=1.CN(C)C=O>[NH2:45][C:44](=[N:46][C:59]([O:60][CH2:61][C:62]([CH3:64])=[CH2:63])=[O:65])[C:43]1[CH:42]=[CH:41][C:40]([NH:39][C@@H:26]([C:27]2[NH:31][C:30](=[O:32])[N:29]([C:33]3[N:34]=[CH:35][CH:36]=[CH:37][N:38]=3)[N:28]=2)[C:15]2[C:14]([F:13])=[C:19]([CH:18]=[C:17]([O:24][CH3:25])[CH:16]=2)[O:20][CH2:21][CH2:22][O:23][C:3](=[O:2])[CH3:4])=[CH:48][CH:47]=1

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 67469869Carbonic acid 2-methylallyl ester 4-nitrophenyl esterHCID 1363340344-{[(R)-[2-fluoro-3-(2-hy droxy ethoxy)-5-methoxyphenyl] (5-oxo-1-pyrimidi n-2-yl-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]amino}benzamidine (R)-methoxyphenylacetate

Product 1

HCID 136334037Acetic acid 2-{3-[(R)-{4-[amino(2-methylallyloxycarbonylimino)methyl]phenylamino}-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy}ethyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-{[(R)-[2-fluoro-3-(2-hy droxy ethoxy)-5-methoxyphenyl] (5-oxo-1-pyrimidi n-2-yl-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]amino}benzamidine (R)-methoxyphenylacetate (0.5 g, 0.755 mmol), carbonic acid 2-methylallyl ester 4-nitrophenyl ester [CAS No. 218598-29-9] (179 mg, 0.755 mmol), and N,N-dimethylformamide (1.5 mL), triethylamine (0.532 mL, 3.78 mmol) was added, and the resulting mixture was stirred overnight at room temperature. To the reaction solution, 4-dimethylaminopyridine (2.78 mg, 0.0228 mmol) and acetic anhydride (0.157 mL, 1.66 mmol) were added, and the resulting mixture was stirred at room temperature for 1 hour and 20 minutes. A buffer of pH 6 was added to the reaction solution, and the resulting mixture was extracted four times with a mixture of ethyl acetate and tetrahydrofuran (ethyl acetate:tetrahydrofuran=1:1). All the organic layers were combined, washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then filtered. The filtrate obtained was concentrated under reduced pressure, after which acetone (3 mL) was added to the residue obtained, and the resulting mixture was stirred at room temperature for 3 days. The precipitated solid was filtered and washed with acetone (1.5 mL). The solid obtained was dried under air flow to obtain the captioned compound (246 mg).

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 1 hour and 20 minutes
  2. additionA buffer of pH 6 was added to the reaction solution
  3. extractionthe resulting mixture was extracted four times
  4. additionwith a mixture of ethyl acetate and tetrahydrofuran (ethyl acetate:tetrahydrofuran=1:1)
  5. washwashed with saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customThe filtrate obtained
  9. concentrationwas concentrated under reduced pressure
  10. additionafter which acetone (3 mL) was added to the residue
  11. customobtained
  12. stirringthe resulting mixture was stirred at room temperature for 3 days
  13. filtrationThe precipitated solid was filtered
  14. washwashed with acetone (1.5 mL)
  15. customThe solid obtained
  16. customwas dried under air flow

Sources & evidence

ORD record
ord-1bc5a8d9685646fcb767536cde5a93a5
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Linked notes

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