(R)-2-methylpyrrolidine L-tartrate → 4-{3-[2-((2R)-2-Methyl-pyrrolidin-1-yl)-ethyl]-cinnolin-7-yl}-benzonitrile

HRID 551572Notes

Reaction equation

C([C@@H]([C@H](C(O)=O)O)O)(O)=O.[CH3:11][C@@H:12]1[CH2:16][CH2:15][CH2:14][NH:13]1.[OH-].[Na+].[Cl-].[Na+].O.Cl[CH2:23][CH2:24][C:25]1[N:26]=[N:27][C:28]2[C:33]([CH:34]=1)=[CH:32][CH:31]=[C:30]([C:35]1[CH:42]=[CH:41][C:38]([C:39]#[N:40])=[CH:37][CH:36]=1)[CH:29]=2>C1(C)C=CC=CC=1>[CH3:11][C@@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH2:23][CH2:24][C:25]1[N:26]=[N:27][C:28]2[C:33]([CH:34]=1)=[CH:32][CH:31]=[C:30]([C:35]1[CH:42]=[CH:41][C:38]([C:39]#[N:40])=[CH:37][CH:36]=1)[CH:29]=2

Participants

Conditions

Temperature: 85 °C

Procedure

(2R)-2-methylpyrrolidine (L)-tartrate (0.100 g, 0.425 mmol) was partitioned between toluene (0.5 mL) and 5 M NaOH/brine (1:1, 1 mL total). The organic phase was then added to the product from Example 169D (0.01 g, 0.034 mmol) and heated to 85° C. in a sealed tube for 48 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 27% yield as a yellow solid. 1H NMR (CD3OD, 300 MHz) δ 8.73 (m, 1H), 8.21 (dd, J=3, 9 Hz, 1H), 8.14 (s, 1H), 8.12 (d, J=9 Hz, 1H), 8.06 (d, J=9 Hz, 2H), 7.92 (d, J=9 Hz, 2H), 3.72-3.48 (m, 4H), 3.15-2.90 (m, 2H), 2.86-2.75 (m, 1H), 2.21-2.10 (m, 1H), 1.98-1.91 (m, 2H), 1.67-1.60 (m, 1H), 1.31 (d, J=6 Hz, 3H). MS (ESI) [M+H]+ at 343.

Workup

temperatureAfter cooling
concentrationthe reaction mixture was concentrated under reduced pressure
custompurified by column chromatography (100% dichloromethane to 95:5 dichloromethane/methanol)
customto afford the product in 27% yield as a yellow solid

Sources & evidence

ORD record: ord-0e82abf90316451d9ff6f9884e8a21de
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07947711B2

Reaction notes

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