Triethylamine → Ethyl 3-[1-(2-{3-Methoxy-4-[(2-toluidinocarbonyl)amino]phenyl}acetyl)-1,2,3,4-tetrahydro-6-quinolinyl]propanoate

HRID 396714Notes

Reaction equation

HRID 396714 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].[NH:24]1[C:33]2[C:28](=[CH:29][C:30]([CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:31][CH:32]=2)[CH2:27][CH2:26][CH2:25]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>O1CCCC1.CN(C)C1C=CN=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([N:24]2[C:33]3[C:28](=[CH:29][C:30]([CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:31][CH:32]=3)[CH2:27][CH2:26][CH2:25]2)=[O:23])[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:11]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114498403-Methoxy-4-o-tolylureidophenylacetic acidHCID 23003903Ethyl 3-(1,2,3,4-tetrahydro-6-quinolinyl)propanoate

Product 1

HCID 23003938Ethyl 3-[1-(2-{3-Methoxy-4-[(2-toluidinocarbonyl)amino]phenyl}acetyl)-1,2,3,4-tetrahydro-6-quinolinyl]propanoate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

A stirred solution of 3-methoxy-4-[3-(2-methylphenyl)ureido]phenylacetic acid (0.232 g, prepared as described in Example 52B of International Patent Application Publication No. WO 96/22966) in anhydrous tetrahydrofuran (5 ml), under an atmosphere of argon and at 20° C., was treated with powdered molecular sieves 4 Å (2 g), ethyl 3-(1,2,3,4-tetrahydro-6-quinolinyl)propanoate (0.115 g, Reference Example 2), triethylamine (0.275 ml), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.223 g) and 4-dimethylaminopyridine (6 mg). After stirring at 20° C. for 1 hour the reaction mixture was filtered through a pad of celite. The filtrate was evaporated under reduced pressure (2.7 kPa) at 40° C. and the residue was treated with ethyl acetate (25 ml). The solution obtained was washed twice with saturated aqueous ammonium chloride solution (5 ml), then with water (5 ml), then dried over magnesium sulfate, and then evaporated under reduced pressure (2.7 kPa) at 40° C. The resulting white foamy solid (0.457 g) was subjected to flash chromatography on silica (0,040-0,063 mm) eluting with a mixture of cyclohexane and ethyl acetate (250 ml, 9:1, then 500 ml, 7:3, then 1000 ml, 4:6; v/v) to give the title compound (0.244 g) as a white foamy solid.

Workup

  1. filtrationwas filtered through a pad of celite
  2. customThe filtrate was evaporated under reduced pressure (2.7 kPa) at 40° C.
  3. additionthe residue was treated with ethyl acetate (25 ml)
  4. customThe solution obtained
  5. washwas washed twice with saturated aqueous ammonium chloride solution (5 ml)
  6. dry with materialwith water (5 ml), then dried over magnesium sulfate
  7. customevaporated under reduced pressure (2.7 kPa) at 40° C
  8. washeluting with a mixture of cyclohexane and ethyl acetate (250 ml, 9:1

Sources & evidence

ORD record
ord-ce17e4befebd4ae7b33857e5758f7165
Source dataset
uspto-grants-2003_08
Patent number
US06608084B1

Reaction notes

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