Triethylamine → methyl 3-chloro-2-[[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido)phenylacetyl]-2-pyrrolidinyl]methoxy]pyridine-5-carboxylate

HRID 354327Notes

Reaction equation

HRID 354327 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[C:37]([O:46][CH2:47][CH:48]2[CH2:52][CH2:51][CH2:50][NH:49]2)=[N:38][CH:39]=[C:40]([C:42]([O:44][CH3:45])=[O:43])[CH:41]=1.CCN(CC)CC>CN(C=O)C.CCOC(C)=O>[Cl:35][C:36]1[C:37]([O:46][CH2:47][CH:48]2[CH2:52][CH2:51][CH2:50][N:49]2[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)=[N:38][CH:39]=[C:40]([C:42]([O:44][CH3:45])=[O:43])[CH:41]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 23512234Methyl 3-chloro-2-[(2-pyrrolidinyl)methoxy]pyridine-5-carboxylateHCID 23512249pentafluorophenyl 3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetate

Product 1

HCID 23512513methyl 3-chloro-2-[[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido)phenylacetyl]-2-pyrrolidinyl]methoxy]pyridine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The mixture of pentafluorophenyl 3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetate (317.0 mg, 0.660 mmol), methyl 3-chloro-2-[(2-pyrrolidinyl)methoxy]pyridine-5-carboxylate (172.0 mg, 0.635 mmol), Et3N (105 ul, 0.756 mmol) in DMF (2.0 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 to afford methyl 3-chloro-2-[[1-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinyl]methoxy]pyridine-5-carboxylate as a brownish oil. To a stirred solution of this compound in THF (6.0 mL) and H2O (2.0 mL) was added LiOH (45.3 mg, 1.89 mmol), and the reaction mixture was stirred for 5 hr at room temp. The mixture was diluted with n-hexane and extracted with 1N-NaOH. The aqueous layer was acidified by the addition of 1N HCl and extracted with CHCl3. The extract was washed with brine, dried over Na2SO4. The solvent was removed under a reduced pressure and the obtained crude solid was recrystallized from n-hexane-EtOAc—EtOH to afford 242.2 mg (70%) 47 as an orange crystalline powder. mp 122-125; IR (KBr) 3354, 1709, 1593, 1535, 1454, 1257 cm−1; 1H-NMR (400 MHz, DMSO-d6) δ1.67-2.03 (m, 4H), 2.50 (s, 3H), 3.33-3.42 (m, 1H), 3.52 (m, 2H), 3.58 (d, J=4.4 Hz, 1H), 3.83 (s, 3H), 4.27-4.31 (m, 2H), 4.42-4.47 (m, 1H), 6.73 (d, J=7.8 Hz, 1H), 6.87-6.95 (m, 3H), 7.11-7.17 (m, 2H), 7.79 (d, J=8.3 Hz, 1H), 7.99 (d, J=8.3 Hz, 1H), 8.14 (dd, J=2.0, 8.8 Hz, 1H), 8.46 (s, 1H), 8.56 (s, 1H), 8.69 (d, J=2.0 Hz, 1H), 13.06 (br s, 1H); MS (FAB) m/z 553 (M++1); Anal. Calcd. for C28H29ClN4O6: C, 60.81; H, 5.29; N, 10.31. Found: C, 60.98; H, 5.50; N, 9.46.

Workup

  1. washwashed with brine
  2. dry with materialdried over Na2SO4
  3. customThe solvent was removed under a reduced pressure

Sources & evidence

ORD record
ord-f726b14d2ea04266bb15336e3acc1ed0
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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