2-Methylpyrrolidine → 4-{3-[2-((Rac)-2-methyl-pyrrolidin-1-yl)-ethyl]-cinnolin-7-yl}-benzonitrile

HRID 860900Notes

Reaction equation

HRID 860900 reaction equation
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][NH:3]1.Cl[CH2:8][CH2:9][C:10]1[N:11]=[N:12][C:13]2[C:18]([CH:19]=1)=[CH:17][CH:16]=[C:15]([C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=1)[CH:14]=2>>[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:8][CH2:9][C:10]1[N:11]=[N:12][C:13]2[C:18]([CH:19]=1)=[CH:17][CH:16]=[C:15]([C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=1)[CH:14]=2

Participants

3

Reactant 2

HCID 130032-MethylpyrrolidineHCID 671047734-[3-(2-Chloro-ethyl)-cinnolin-7-yl]-benzonitrile

Product 1

HCID 100430304-{3-[2-((Rac)-2-methyl-pyrrolidin-1-yl)-ethyl]-cinnolin-7-yl}-benzonitrileYield 43%

Conditions

Temperature
65 °C

Procedure

Racemic 2-methylpyrrolidine (0.5 mL, neat) was added to the product from Example 169D (0.01 g, 0.034 mmol) and heated to 65° C. in a sealed tube for 18 hours. After cooling, the reaction mixture was concentrated under reduced pressure and purified by column chromatography (100% dichloromethane to 95:5 dichloromethane/methanol) to afford the product in 43% yield as a brown-yellow semi-solid. 1H NMR (CD3OD, 300 MHz) δ 8.72 (m, 1H), 8.20 (dd, J=3, 9 Hz, 1H), 8.16 (s, 1H), 8.11 (d, J=9 Hz, 1H), 8.06 (d, J=9 Hz, 2H), 7.91 (d, J=9 Hz, 2H), 3.58–3.46 (m, 4H), 2.85–2.65 (m, 2H), 2.57–2.51 (m, 1H), 2.03–1.90 (m, 1H), 1–0.89–1.83 (m, 2H), 1.56–1.50 (m, 1H), 1.21 (d, J=6 Hz, 3H). MS (ESI) [M+H]+ at 343.

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. custompurified by column chromatography (100% dichloromethane to 95:5 dichloromethane/methanol)
  4. customto afford the product in 43% yield as a brown-yellow semi-solid

Sources & evidence

ORD record
ord-2e23d4278ee1459498c6a018b20beedc
Source dataset
uspto-grants-2006_12
Patent number
US07153889B2

Reaction notes

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