Triethylamine → HCID 59694104, compound

HRID 899854Notes

Reaction equation

HRID 899854 reaction equation
[Cl:1][C:2]1[CH:10]=[N:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[N:20]=[C:19]1[CH2:27][N:28]([CH:33]1[C:42]2[N:41]=[CH:40][CH:39]=[CH:38][C:37]=2[CH2:36][CH2:35][CH2:34]1)[CH2:29][CH2:30][CH2:31][NH2:32].CCN(CC)CC>C(Cl)Cl.CN(C=O)C.C1COCC1>[NH:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[N:20]=[C:19]1[CH2:27][N:28]([CH:33]1[C:42]2[N:41]=[CH:40][CH:39]=[CH:38][C:37]=2[CH2:36][CH2:35][CH2:34]1)[CH2:29][CH2:30][CH2:31][NH:32][C:4](=[O:6])[C:3]1[C:7]([Cl:11])=[CH:8][N:9]=[CH:10][C:2]=1[Cl:1]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 6057633,5-Dichloroisonicotinic acidHCID 10308735HCID 10308735, compound

Product 1

HCID 59694104HCID 59694104, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 3,5-dichloro-isonicotinic acid (52 mg, 0.27 mmol) in CH2Cl2 (1.1 mL) cooled to 0° C. was added oxalyl chloride (70 μL, 0.81 mmoL) and DMF (1 drop) and the resulting mixture was stirred at 0° C. for 5 minutes and at room temperature for 1.5 hours. The mixture was concentrated under reduced pressure and dried in vacuo for 5 minutes. To the resulting beige solid in THF (3 mL) was added N1-(1H-benzoimidazol-2-ylmethyl)-N1-(5,6,7,8-tetrahydro-quinolin-8-yl)-propane-1,3-diamine from above (100 mg, 0.30 mmol) and Et3N (76 μL, 0.54 mmol) and the resulting mixture was stirred at room temperature for 3 hours. The mixture was concentrated under reduced pressure, diluted with EtOAc (40 mL) and washed consecutively with saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL). The organic phase was dried (MgSO4), filtered, and concentrated under reduced pressure. Purification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 100:1:1) afforded COMPOUND 153 (55 mg, 40%) as a white foam. 1H NMR (CDCl3) δ 1.70-1.94 (m, 4H), 2.04-2.15 (m, 1H), 2.26-2.33 (m, 1H), 2.64-2.96 (m, 4H), 3.10-3.15 (m, 1H), 3.68 (d, 1H, J=15.6 Hz), 3.80 (d, 1H, J=15.6 Hz), 3.98-4.07 (m, 1H), 4.19-4.25 (m, 1H), 6.83 (dd, 1H, J=7.8, 4.8 Hz), 7.20-7.23 (m, 2H), 7.35-7.40 (m, 2H), 7.66-7.68 (m, 2H), 8.34 (s, 2H), 8.78 (br s, 1H); 13C NMR (CDCl3) δ 21.69, 21.92, 26.70, 29.38, 39.04,49.41, 49.87, 59.45, 111.10, 119.37, 122.63, 122.95, 129.27, 135.68, 138.29, 143.68, 146.10, 147.70, 154.94, 157.51. 162.27. ES-MS m/z 510 (M+H). Anal. Calcd. for C26H26N6Cl2O.0.3CH2Cl2.0.1H2O: C, 58.86; H, 5.03; N, 15.66; Cl, 17.17. Found: C, 59.22; H, 5.21; N, 15.74; Cl, 16.80.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customdried in vacuo for 5 minutes
  3. stirringthe resulting mixture was stirred at room temperature for 3 hours
  4. concentrationThe mixture was concentrated under reduced pressure
  5. additiondiluted with EtOAc (40 mL)
  6. washwashed consecutively with saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL)
  7. dry with materialThe organic phase was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 100:1:1)

Sources & evidence

ORD record
ord-1d57effa782846608dca9efd57771878
Source dataset
uspto-grants-2008_04
Patent number
US07354934B2

Reaction notes

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