pentafluorophenyl 3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetate → HCID 69333000, compound

HRID 350386Notes

Reaction equation

HRID 350386 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].[F:35][CH:36]1[CH2:40][NH:39][CH:38]([CH2:41][O:42][C:43]2[CH:53]=[CH:52][C:46]([C:47]([O:49][CH2:50][CH3:51])=[O:48])=[CH:45][C:44]=2[O:54][CH3:55])[CH2:37]1>CN(C=O)C.CCOC(C)=O>[F:35][CH:36]1[CH2:40][N:39]([C:21](=[O:23])[CH2:20][C:5]2[CH:6]=[CH:7][C:8]([NH:9][C:10]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[CH3:19])=[O:11])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH:38]([CH2:41][O:42][C:43]2[CH:53]=[CH:52][C:46]([C:47]([O:49][CH2:50][CH3:51])=[O:48])=[CH:45][C:44]=2[O:54][CH3:55])[CH2:37]1

Participants

5

Reactant 2

HCID 23512249pentafluorophenyl 3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetateHCID 23512277Ethyl 4-(4-fluoro-2-pyrrolidinyl)methoxy-3-methoxybenzoate

Product 1

HCID 69333000HCID 69333000, compoundYield 100.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of pentafluorophenyl 3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetate (404.0 mg, 0.840 mmol), ethyl 4-(4-fluoro-2-pyrrolidinyl)methoxy-3-methoxybenzoate (250.0 mg, 0.840 mmol), Et3 N (141 μl, 1.009 mmol) in DMF (4.0 mL) was stirred for 1 hr at room temp. The mixture was diluted with EtOAc, washed with water, 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 (1:3, v/v) to afford 502 mg (q.y.) of ethyl 4-[[4-fluoro-1-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinyl]methoxy]-3-methoxybenzoate as a yellow oil. To a stirred solution of this compound in THF (8.0 mL) and H2O (2.0 mL) was added LiOH (60.4 mg, 2.520 mmol), and the mixture was stirred at room temp. overnight, and 50° C. for 1 day. The mixture was diluted with CHCl3, and extracted with 1 N NaOH. The aqueous layer was acidified by the addition of 1 N HCl and extracted with CHCl3. The extract was washed with brine and dried over Na2SO4. The solvent was removed under a reduced pressure and the obtained crude solid was recrystallized from EtOAc—CHCl3-EtOH-n-hexane to afford 294.8 mg (62%) 45 as a white crystalline powder. IR (KBr) 2958, 2937, 1687, 1601, 1531, 1454, 1419, 1267, 1214, 1029 cm−1; 1H-NMR (400 MHz, DMSO-d6) δ 1.86–2.09 (m, 5H), 2.06 (s, 3H), 2.25 (s, 3H), 3.47–3.67 (m, 6H), 3.76 (s, 3H), 4.05–4.12 (m, 2H), 4.30–4.31 (m, 1H), 6.51 (s, 1H), 6.55 (s, 1H), 6.73–6.95 (m, 2H), 7.11–7.17 (m, 2H), 7.64 (s, 1H), 7.79 (d, J=7.8 Hz, 1H), 7.99 (d, J=7.8 Hz, 1H), 8.47 (s, 1H), 8.55 (s, 1H); MS (FAB) m/z 566 (M++1); Anal. Calcd for C30H32FN3O7.1/2H2O: C, 62.71; H. 5.79; F, 3.31; N, 7.31. Found: C, 63.13; H. 6.17; F, 3.12; N, 7.04.

Workup

  1. washwashed with water, 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 (1:3

Sources & evidence

ORD record
ord-4d7f01e517544407876f23a20dcf1895
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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