Dimethylformamide → 3-methoxy-2,2-dimethylpropionic acid 5-[[3-(2-acetoxyethoxy)-2-fluoro-5-methoxyphenyl]-(4-{amino[2-methylall yloxycarbonylimino]methyl}phenylamino)methyl]-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester

HRID 2089639

Reaction equation

HRID 2089639 reaction equation
C(O)(=O)C.[C:5]([O:8][CH2:9][CH2:10][O:11][C:12]1[C:13]([F:53])=[C:14]([CH:20]([NH:43][C:44]2[CH:49]=[CH:48][C:47]([C:50](=[NH:52])[NH2:51])=[CH:46][CH:45]=2)[C:21]2[N:22]=[C:23]([O:32][CH2:33][O:34][C:35](=[O:42])[C:36]([CH3:41])([CH3:40])[CH2:37][O:38][CH3:39])[N:24]([C:26]3[N:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[N:25]=2)[CH:15]=[C:16]([O:18][CH3:19])[CH:17]=1)(=[O:7])[CH3:6].C(N(CC)CC)C.[N+](C1C=CC([O:70][C:71](=O)[O:72][CH2:73][C:74]([CH3:76])=[CH2:75])=CC=1)([O-])=O.CN(C=O)C>O.C(OCC)(=O)C>[C:5]([O:8][CH2:9][CH2:10][O:11][C:12]1[C:13]([F:53])=[C:14]([CH:20]([NH:43][C:44]2[CH:49]=[CH:48][C:47]([C:50]([NH2:51])=[N:52][C:71]([O:72][CH2:73][C:74]([CH3:76])=[CH2:75])=[O:70])=[CH:46][CH:45]=2)[C:21]2[N:22]=[C:23]([O:32][CH2:33][O:34][C:35](=[O:42])[C:36]([CH3:41])([CH3:40])[CH2:37][O:38][CH3:39])[N:24]([C:26]3[N:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[N:25]=2)[CH:15]=[C:16]([O:18][CH3:19])[CH:17]=1)(=[O:7])[CH3:6]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 67469869Carbonic acid 2-methylallyl ester 4-nitrophenyl esterHCID 674699453-methoxy-2,2-dimethylpropionic acid 5-[[3-(2-acetoxyethoxy)-2-fluoro-5-methoxyphenyl]-(4-carbamimidoylphen ylamino)methyl]-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester acetate

Product 1

HCID 682128653-methoxy-2,2-dimethylpropionic acid 5-[[3-(2-acetoxyethoxy)-2-fluoro-5-methoxyphenyl]-(4-{amino[2-methylall yloxycarbonylimino]methyl}phenylamino)methyl]-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl esterYield 95.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-methoxy-2,2-dimethylpropionic acid 5-[[3-(2-acetoxyethoxy)-2-fluoro-5-methoxyphenyl]-(4-carbamimidoylphen ylamino)methyl]-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester acetate (13 mg), triethylamine (0.0074 mL), carbonic acid 2-methylallyl ester 4-nitrophenyl ester (5.6 mg), and DMF (2 mL) was stirred for 3 days at room temperature. The resulting mixture was poured into ethyl acetate (100 mL) and water (30 mL). After shaking the mixture, the organic layer was collected, sequentially washed twice with water (30 mL) and with saturated aqueous sodium chloride solution (30 mL), and dried over anhydrous magnesium sulfate. The resulting mixture was filtered, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate) to obtain the captioned compound (13 mg).

Workup

  1. stirringAfter shaking the mixture
  2. customthe organic layer was collected
  3. washsequentially washed twice with water (30 mL) and with saturated aqueous sodium chloride solution (30 mL)
  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 purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate)

Sources & evidence

ORD record
ord-6455d7621b8f4b77aa4eb43a07109cc6
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Linked notes

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