Triethylamine → HCID 178519333, compound

HRID 1017725Notes

Reaction equation

HRID 1017725 reaction equation
[O:1]=[C:2]1[C:11]([C:12]2[NH:16][C:15]3[CH:17]=[CH:18][C:19]([C:21]([OH:23])=O)=[CH:20][C:14]=3[N:13]=2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.[N:24]1(C(OC(C)(C)C)=O)[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[N:24]1([C:21]([C:19]2[CH:18]=[CH:17][C:15]3[NH:16][C:12]([C:11]4[C:2](=[O:1])[NH:3][C:4]5[C:9]([CH:10]=4)=[CH:8][CH:7]=[CH:6][CH:5]=5)=[N:13][C:14]=3[CH:20]=2)=[O:23])[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178524150HCID 178524150, compound

Product 1

HCID 178519333HCID 178519333, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

A mixture of 2-(2-oxo-1,2-dihydro-3-quinolinyl)-1H-benzimidazole-5-carboxylic acid (4-6, 130 mg, 0.43 mmol, 1 equiv, tert-butyl l-piperazinecarboxylate (79 mg, 0.43 mmol, 1.0 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (97 mg, 0.51 mmol, 1.2 equiv), 1-hydroxy-7-azabenzotriazole (70 mg, 0.51 mmol, 1.2 equiv), and triethylamine (0.148 mL, 1.06 mmol, 2.50 equiv) in DMF (5.0 mL) was stirred at 23° C. for 20 h. The reaction mixture was partitioned between water (50 mL) ethyl actate (3×50 mL). The combined organic layers were dried over sodium sulfate and concentrated. A solution of the residue, DMSO (10 uL), and water (10 uL) in a 1:1 mixture of dichloromethane and trifluoroacetic acid (20 mL) was stirred at 23° C. for 45 min. The reaction mixture was concentrated, and the residue was purified by reverse-phase liquid chromotography (H2O/CH3CN gradient w/0.1% TFA present). The desired fractions were partitioned between saturated sodium bicarbonate solution (50 mL) and a 10% solution of methanol in dichloromethane (2×50 mL) to provide 3-[5-(1-piperazinylcarbonyl)-1H-benzimidazol-2-yl]-2(1H)-quinolinone (14-1) as its free base. 1H NMR (500 MHz, DMSO-d6) δ 11.83 (s, 1H), 8.59 (s, 1H), 7.74 (m, 2H), 7.53 (m, 2H), 7.39 (m, 2H), 7.26 (m, 2H), 3.61 (br m, 1H), 3.60 (br m, 1H), 3.32 (br m, 1H), 1.98 (br m, 1H), 1.89 (br m, 1H), 1.62 (br m, 2H).

Workup

  1. customThe reaction mixture was partitioned between water (50 mL) ethyl actate (3×50 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated
  4. additionA solution of the residue, DMSO (10 uL), and water (10 uL) in a 1:1 mixture of dichloromethane and trifluoroacetic acid (20 mL)
  5. stirringwas stirred at 23° C. for 45 min
  6. concentrationThe reaction mixture was concentrated
  7. customthe residue was purified by reverse-phase liquid chromotography (H2O/CH3CN gradient w/0.1% TFA present)
  8. customThe desired fractions were partitioned between saturated sodium bicarbonate solution (50 mL)

Sources & evidence

ORD record
ord-012a61e988434ffbbe2e39e281398aa5
Source dataset
uspto-grants-2002_11
Patent number
US06479512B1

Reaction notes

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