Triethylamine → HCID 67690889, compound

HRID 484443

Reaction equation

HRID 484443 reaction equation
Cl.[CH3:2][O:3][C:4]([CH:6]1[CH2:15][CH:14]([NH2:16])[C:13]2[C:8](=[CH:9][C:10]([Cl:18])=[CH:11][C:12]=2[Cl:17])[NH:7]1)=[O:5].C(N(CC)CC)C.[C:26]([O:30][C:31]([NH:33][CH2:34][C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=1)[C:38](O)=[O:39])=[O:32])([CH3:29])([CH3:28])[CH3:27].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl>[CH3:2][O:3][C:4]([C@H:6]1[CH2:15][C@H:14]([NH:16][C:38]([C:37]2[CH:41]=[CH:42][CH:43]=[C:35]([CH2:34][NH:33][C:31]([O:30][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:32])[CH:36]=2)=[O:39])[C:13]2[C:8](=[CH:9][C:10]([Cl:18])=[CH:11][C:12]=2[Cl:17])[NH:7]1)=[O:5]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27559293-(((tert-Butoxycarbonyl)amino)methyl)benzoic acidHCID 19747381HCID 19747381, compound

Product 1

HCID 67690889HCID 67690889, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-methoxycarbonyl-5,7-dichloro-4-amino-1,2,3,4-tetrahydroquinoline hydrochloride (Example 9) (300 mg, 0.963 mmol) in anhydrous dichloromethane (15 ml) under an atmosphere of nitrogen was added dry triethylamine (403 μl, 2.89 mol) and the resulting mixture was stirred at room temperature for 5 min. To this was added 3-(tertbutyloxycarbonylamino)methyl benzoic acid (step a) (290 mg, 1.16 mmol), 1-hydroxybenzotriazole (156 mg, 1.16 mol) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (222 mg, 1.16 mmol) and stirring was continued for approximately 18 h. The mixture was then concentrated in vacuo and the residue partitioned between ethyl acetate (100 ml) and 0.5M citric acid (150 ml). The organic layer was retained and washed successively with 0.5M citric acid (150 ml), saturated sodium bicarbonate solution (2×150 ml) and brine (100 ml) before drying (Na2SO4). The solvent was removed and the residue was recrystallised from ethyl acetate/hexane to give the title compound as colourless crystals (351 mg), m.p. 222°-223° C. δ (DMSO, 250 MHz) 1.39 (9H, s, C(CH3)3), 1.78 (1H, ddd, J=12.8, 12.6 and 3.9 Hz, CHACHBHCCHD), 2.26 (1H, dm, J=12.8 Hz, CHACHBHCCHD), 3.71 (3H, s, COOCH3), 4.05 (1H, dd, J=13.0 and 3.0 Hz, CHACHBHCCHD), 4.14 (2H, d, J=5.8 Hz, ArCH2NH), 5.26 (1H, m, CHACHBHCCHD), 6.69 (1H, d, J=2.1 Hz, 6-H or 8-H), 6.90 (1H, d, J=2.1 Hz, 6-H or 8-H), 6.93 (1H, s, ArNHCH), 7.37 (3H, m, Ar-H and CH2NHCO), 7.71-7.76 (2H, m, Ar-H), 8.68 (1H, d, J=7.1 Hz); m/e 507 (M+), 198 (100%, M-H, CO2CH2CH3,NHCOC6H4CH2NHCOOC(CH3)3).

Workup

  1. stirringstirring
  2. waitwas continued for approximately 18 h
  3. concentrationThe mixture was then concentrated in vacuo
  4. customthe residue partitioned between ethyl acetate (100 ml) and 0.5M citric acid (150 ml)
  5. washwashed successively with 0.5M citric acid (150 ml), saturated sodium bicarbonate solution (2×150 ml) and brine (100 ml)
  6. dry with materialbefore drying (Na2SO4)
  7. customThe solvent was removed
  8. customthe residue was recrystallised from ethyl acetate/hexane

Sources & evidence

ORD record
ord-c88457d213424b3ba7f771d9f5628dcb
Source dataset
uspto-grants-1993_07
Patent number
US05231102

Linked notes

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