Triethylamine → HCID 69832616, compound

HRID 1266458Notes

Reaction equation

HRID 1266458 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].[CH2:24]([O:26][C:27]([CH:29]1[CH:33]([C:34]2[CH:39]=[CH:38][C:37]([NH2:40])=[CH:36][CH:35]=2)[CH2:32][N:31]([C:41](=[O:48])[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH2:30]1)=[O:28])[CH3:25].C(N(CC)CC)C.CN(C1C=CC=CN=1)C>O1CCCC1.CN(C)C=O>[CH2:24]([O:26][C:27]([CH:29]1[CH:33]([C:34]2[CH:39]=[CH:38][C:37]([NH:40][C:21](=[O:23])[CH2:20][C:5]3[CH:6]=[CH:7][C:8]([NH:9][C:10]([NH:12][C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[CH3:19])=[O:11])=[C:3]([O:2][CH3:1])[CH:4]=3)=[CH:36][CH:35]=2)[CH2:32][N:31]([C:41](=[O:48])[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:30]1)=[O:28])[CH3:25]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 114498403-Methoxy-4-o-tolylureidophenylacetic acidHCID 69832931Ethyl 4-(4-aminophenyl)-1-benzoyl-3-pyrrolidinecarboxylate

Product 1

HCID 69832616HCID 69832616, compoundYield 93.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of [3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetic acid (5.1 g) in anhydrous tetrahydrofuran (140 ml), at 23° C. and under an atmosphere of argon, was treated with benzotriazol-lyloxytris(dimethylamino)phosphonium hexafluorophosphate (8.61 g). After stirring for 1 hour the mixture was treated with 1-benzoyl-4-(4-amino-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester (5.48 g, Reference Example 8) then with triethylamine (9.1 ml), dimethylaminopyridine (0.2 g) and dimethylformamide (5 ml). The resulting mixture was stirred at 23° C. for 2 days then evaporated (40° C. and 2.7 kPa). The residue was treated with ethyl acetate (300 ml) and the resulting solution was washed twice with water (200 ml), twice with hydrochloric acid (200 ml, 1N), then twice with aqueous sodium bicarbonate solution (200 ml, 10%), then with brine (100 ml), then with water (100 ml), then dried over magnesium sulphate and then evaporated (40° C. and 2.7 kPa). The resulting white meringue was triturated with diethyl ether (50 ml) for 20 hours affording the title compound (9.6 g) as a white powder, m.p. 130° C. 1H-NMR [500 MHz, (CD3)2SO at 383° K.]: δ 1.15 (t, J=7 Hz, 3H); 2.30 (s, 3H); 3.33 (m, 1H); 3.50 to 3.70 (m, 2H); 3.62 (s, 2H); 3.77 (m, 1H); 3.85 to 4.00 (m, 2H); 3.91 (s, 3H); 4.10 (q, J=7 Hz, 2H); 6.89 (bd, J=8 Hz, 1H); 6.95 to 7.05 (m, 1H); 7.04 (d, J=2 Hz, 1H); 7.15 (t, J=8 Hz, 1H); 7.20 (d, J=7.5 Hz, 1H); 7.25 (d, J=8 Hz, 2H); 7.45 (m, 3H); 7.54 (m, 4H); 7.69 (d, J=8 Hz, 1H); 8.01 (d, J=8 Hz, 1H); 8.16 (s, 1H); 8.22 (s, 1H); 9.56 (s, 1H). MS [DCI (reactant gas, ammonia)]: 635[M+H]+.

Workup

  1. stirringThe resulting mixture was stirred at 23° C. for 2 days
  2. customthen evaporated (40° C. and 2.7 kPa)
  3. additionThe residue was treated with ethyl acetate (300 ml)
  4. washthe resulting solution was washed twice with water (200 ml), twice with hydrochloric acid (200 ml, 1N)
  5. dry with materialtwice with aqueous sodium bicarbonate solution (200 ml, 10%), then with brine (100 ml), then with water (100 ml), then dried over magnesium sulphate
  6. customevaporated (40° C. and 2.7 kPa)
  7. customThe resulting white meringue was triturated with diethyl ether (50 ml) for 20 hours

Sources & evidence

ORD record
ord-2425cc5418d2444c94817c873e3b0aea
Source dataset
uspto-grants-2003_04
Patent number
US06548533B2

Reaction notes

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