4-Methoxyphenylacetic Acid → HCID 22405583, compound

HRID 441182Notes

Reaction equation

HRID 441182 reaction equation
[NH2:1][C:2]1[C:3](=[O:35])[N:4]([CH2:14][C:15]([NH:17][CH:18]([CH:32]([CH3:34])[CH3:33])[CH:19]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[C:20]([F:23])([F:22])[F:21])=[O:16])[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.[CH3:36][O:37][C:38]1[CH:43]=[CH:42][C:41]([CH2:44][C:45](O)=[O:46])=[CH:40][CH:39]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl.CN(C)CCCC(N=C=NCC)CC.ON1C2C=CC=CC=2N=N1>O1CCCC1.CN(C)C1C=CN=CC=1.C(OCC)(=O)C.C(N(CC)CC)C>[Si:25]([O:24][CH:19]([C:20]([F:23])([F:21])[F:22])[CH:18]([NH:17][C:15](=[O:16])[CH2:14][N:4]1[C:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][CH:7]=[C:2]([NH:1][C:45](=[O:46])[CH2:44][C:41]2[CH:42]=[CH:43][C:38]([O:37][CH3:36])=[CH:39][CH:40]=2)[C:3]1=[O:35])[CH:32]([CH3:33])[CH3:34])([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:27])[CH3:26]

Participants

11

Reactant 6

HCID 76904-Methoxyphenylacetic AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 10391657HCID 10391657, compoundHCID 22405558HCID 22405558, compound

Product 1

HCID 22405583HCID 22405583, compoundYield 61.8%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To 2-(3-amino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)acetamide (0.295 g) suspended in redistilled tetrahydrofuran (5 mL) was added 4-methoxyphenylacetic acid (0.97 g), followed by 1-hydroxybenzotriazole hydrate (0.156 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.123 g). The reaction was shown by TLC to be incomplete after overnight stirring; therefore, triethylamine (0.08 mL) and 4-dimethylaminopyridine (catalytic amount) were added to the mixture. After stirring 1 h, additional acid (0.098 g), 1-(3-dimethylaminopropylpropyl)-3-ethylcarbodiimide hydrochloride (0.123 g), triethylamine (0.08 mL), and 1-hydroxybenzotriazole (0.156 g) were added. Additional tetrahydrofuran (2 mL) was added to facilitate stirring. After stirring overnight TLC indicated little change in the reaction mixture which was diluted with ethyl acetate (50 mL); washed with water (twice), saturated aqueous sodium bicarbonate (three times) and brine; dried; and evaporated. Purification by chromatography, eluting with ethanol:ethyl acetate:dichloromethane (0.5:5:94.5) gave N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)-2-[3-(4-methoxyphenyl)acetylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl]acetamide (0.235 g); TLC (of crude reaction mixture): Rf =0.88, methanol:dichloromethane (4:96); MS: m/z=660(M+1).

Workup

  1. stirringAfter stirring 1 h
  2. stirringto facilitate stirring
  3. stirringAfter stirring overnight TLC
  4. washwashed with water (twice), saturated aqueous sodium bicarbonate (three times) and brine
  5. customdried
  6. customand evaporated
  7. customPurification by chromatography
  8. washeluting with ethanol:ethyl acetate:dichloromethane (0.5:5:94.5)

Sources & evidence

ORD record
ord-698f7f7f39c1410ab0ce7754b1abdf99
Source dataset
uspto-grants-1996_05
Patent number
US05521179

Reaction notes

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