Triethylamine → methyl 3,5-dichloro-4-[[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinyl]methoxy]benzoate

HRID 354294Notes

Reaction equation

HRID 354294 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([O:23]C2C(F)=C(F)C(F)=C(F)C=2F)=O)[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11].[Cl:35][C:36]1[CH:37]=[C:38]([CH:43]=[C:44]([Cl:53])[C:45]=1[O:46][CH2:47][CH:48]1[CH2:52][CH2:51][CH2:50][NH:49]1)[C:39]([O:41][CH3:42])=[O:40].CCN(CC)CC>CN(C=O)C.CCOC(C)=O>[Cl:35][C:36]1[CH:37]=[C:38]([CH:43]=[C:44]([Cl:53])[C:45]=1[O:46][CH2:47][CH:48]1[CH2:52][CH2:51][CH2:50][N:49]1[C:21](=[O:23])[CH2:20][C:5]1[CH:6]=[CH:7][C:8]([NH:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])=[O:11])=[C:3]([O:2][CH3:1])[CH:4]=1)[C:39]([O:41][CH3:42])=[O:40]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 23512157Methyl 3,5-dichloro-4-(2-pyrrolidinyl)methoxybenzoateHCID 23512249pentafluorophenyl 3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetate

Product 1

HCID 23512540methyl 3,5-dichloro-4-[[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinyl]methoxy]benzoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of pentafluorophenyl 3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetate (385.8 mg, 0.803 mmol), methyl 3,5-dichloro-4-(2-pyrrolidinyl)methoxybenzoate (244.3 mg, 0.803 mmol), Et3N (0.13 mL, 0.964 mmol) in DMF (4 mL) was stirred for 1 hr at room temp. The mixture was diluted with EtOAc, washed with brine, and dried over Na2SO4. The solvent was removed under a reduced pressure, and the residue was chromatographed on silica-gel with n-hexane:EtOAc (1:2, v/v) as eluent to afford methyl 3,5-dichloro-4-[[1-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinyl]methoxy]benzoate as an oil. To a stirred solution of this compound in THF (8 mL) and H2O (2 mL) was added LiOH (57.7 mg, 2.409 mmol), and the mixture was stirred at room temp overnight. The tire was concentrated in vacuo, and the residue was diluted with CHCl3. The solution was washed with 1N HCl, brine, and dried over Na2SO4. The solvent was removed under a reduced pressure, and the obtained crude solid was recrystallized from n-hexane-MeOH—CHCl3 to afford 428.2 mg (91%) 30 as a white crystalline powder. IR (KBr) 1618, 1535, 1454, 1257, 754 cm−1; 1H-NMR (400 MHz, DMSO-d6) δ1.83-2.24 (m, 4H), 2.24 (s, 3H), 3.50-3.58 (m, 4H), 3.84 (s, 3H), 3.98-4.05 (m, 1H), 4.15 (dd, J=2.9, 8.7 Hz, 1H), 4.29 (br m, 1H), 6.74 (d, J=8.3 Hz, 1H), 6.87 (s, 1H), 6.93 (t, J=7.3 Hz, 1H), 7.11 (d, J=7.8 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 7.79 (d, J=8.3 Hz, 1H), 7.86 (s, 1H), 7.87 (d, J=9.8 Hz, 1H), 7.99 (d, J=8.3 Hz, 1H), 8.49 (s, 1H), 8.58 (s, 1H); MS (FAB) m/z 586 (M++1).

Workup

  1. washwashed with brine
  2. dry with materialdried over Na2SO4
  3. customThe solvent was removed under a reduced pressure
  4. customthe residue was chromatographed on silica-gel with n-hexane:EtOAc (1:2

Sources & evidence

ORD record
ord-4610f4860e46404e81ceffdc8098dd03
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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