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

HRID 2089708Notes

Reaction equation

HRID 2089708 reaction equation
C(O)(=O)C.[C:5]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C@@H:15]([C:32]2[N:36]=[C:35]([O:37][CH2:38][O:39][C:40]([O:42][CH:43]([CH3:45])[CH3:44])=[O:41])[N:34]([C:46]3[N:51]=[CH:50][CH:49]=[CH:48][N:47]=3)[N:33]=2)[C:16]2[C:17]([F:31])=[C:18]([CH:26]=[C:27]([O:29][CH3:30])[CH:28]=2)[O:19][CH2:20][CH2:21][O:22][C:23](=[O:25])[CH3:24])=[CH:10][CH:9]=1)(=[NH:7])[NH2:6].CN(C=O)C.[N+]([C:60]1C=C[C:63]([O:66][C:67](=O)[O:68]CCCC)=[CH:62][CH:61]=1)([O-])=O.C(N(CC)CC)C>O.C(OCC)(=O)C>[NH2:7][C:5](=[N:6][C:67]([O:66][CH2:63][CH2:62][CH2:61][CH3:60])=[O:68])[C:8]1[CH:9]=[CH:10][C:11]([NH:14][C@@H:15]([C:32]2[N:36]=[C:35]([O:37][CH2:38][O:39][C:40]([O:42][CH:43]([CH3:45])[CH3:44])=[O:41])[N:34]([C:46]3[N:47]=[CH:48][CH:49]=[CH:50][N:51]=3)[N:33]=2)[C:16]2[C:17]([F:31])=[C:18]([CH:26]=[C:27]([O:29][CH3:30])[CH:28]=2)[O:19][CH2:20][CH2:21][O:22][C:23](=[O:25])[CH3:24])=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 12867351Butyl 4-nitrophenyl carbonateHCID 86677426HCID 86677426, compound

Product 1

HCID 86677425Acetic acid 2-{3-[(R)-(4-{amino[butoxycarbonylimino]methyl}phenylamino)-(5-isopropoxycarbonyloxymethoxy-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy)ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of Acetic acid 2-{3-[(R)-(4-carbamimidoylphenylamino)-(5-isopropoxycarbonyloxymethoxy-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy}ethyl ester acetic acid salt (23 mg) obtained in Example 67a and DMF (1 ml), carbonic acid butyl ester 4-nitrophenyl ester [CAS No. 67036-13-9] (10 mg) and triethylamine (50 μl) were added, and the resulting mixture was stirred at room temperature for 63 h. Ethyl acetate and water were added to the mixture, and the organic layer was collected. The organic layer was sequentially washed with water and with saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The desiccant was filtered off, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate) to obtain the captioned compound (16.80 mg).

Workup

  1. customthe organic layer was collected
  2. washThe organic layer was sequentially washed with water and with saturated aqueous sodium chloride solution
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationThe desiccant was filtered off
  5. customthe filtrate obtained
  6. concentrationwas concentrated under reduced pressure
  7. customThe residue obtained
  8. customwas purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate)

Sources & evidence

ORD record
ord-35ee7317617b49569393fd7564063ee2
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Reaction notes

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