Triethylamine → HCID 69833704, compound

HRID 1266462Notes

Reaction equation

HRID 1266462 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([OH:23])=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].[CH3:24][O:25][C:26]([CH:28]1[CH2:32][CH2:31][N:30]([C:33](=[O:40])[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:29]1[C:41]1[CH:46]=[CH:45][C:44]([NH2:47])=[CH:43][CH:42]=1)=[O:27].[CH2:48](N(CC)CC)C.CN(C1C=CC=CN=1)C>O1CCCC1>[CH2:24]([O:25][C:26]([CH:28]1[CH2:32][CH2:31][N:30]([C:33](=[O:40])[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:29]1[C:41]1[CH:42]=[CH:43][C:44]([NH:47][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:45][CH:46]=1)=[O:27])[CH3:48]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 114498403-Methoxy-4-o-tolylureidophenylacetic acidHCID 69832937HCID 69832937, compound

Product 1

HCID 69833704HCID 69833704, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of [3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetic acid (1.35 g, prepared as described in Example 52B of International Patent Application Publication No. WO 96/22966) in anhydrous tetrahydrofuran (60 ml), at 20° C. and under an atmosphere of argon, was treated with benzotriazol-lyloxytris(dimethylamino)phosphonium hexafluorophosphate (2.04 g). After stirring for 10 minutes the mixture was treated with 2-(4-amino-phenyl)-1-benzoyl-pyrrolidine-3-carboxylic acid methyl ester (1.5 g, Reference Example 14) then with triethylamine (1.77 ml) and dimethylaminopyridine (0.051 g). The resulting mixture was stirred at 20° C. for 60 hours then evaporated (40° C. and 2.7 kPa). The residue was dissolved in ethyl acetate (150 ml) and the solution was washed with water (100 ml), then with aqueous potassium bicarbonate solution (100 ml, 10%), then with water (50 ml), then dried over magnesium sulphate and then evaporated under reduced pressure (40° C., 2.7 kPa). The residue was subjected to flash chromatography on silica (200 g, 0.045-0.020 mm particle size) eluting with a mixture of cyclohexane and ethyl acetate (30:70, v/v) affording the title compound (0.33 g) as an off-white powder. MS [DCI (reactant gas, ammonia)]: 621 [M+H]+.

Workup

  1. stirringThe resulting mixture was stirred at 20° C. for 60 hours
  2. customthen evaporated (40° C. and 2.7 kPa)
  3. dissolutionThe residue was dissolved in ethyl acetate (150 ml)
  4. washthe solution was washed with water (100 ml)
  5. dry with materialwith aqueous potassium bicarbonate solution (100 ml, 10%), then with water (50 ml), then dried over magnesium sulphate
  6. customevaporated under reduced pressure (40° C., 2.7 kPa)
  7. washeluting with a mixture of cyclohexane and ethyl acetate (30:70

Sources & evidence

ORD record
ord-6580f7b2e1424ca59d8976e480814743
Source dataset
uspto-grants-2003_04
Patent number
US06548533B2

Reaction notes

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