N-Methyl-L-proline

ChEBI: An L-proline derivative obtained by replacement of the amino hydrogen by a methyl group.

N-methylproline is an L-proline derivative obtained by replacement of the amino hydrogen by a methyl group. It has a role as a plant metabolite and a human metabolite. It is a L-proline derivative and a tertiary amino compound. It is a tautomer of a N-methylproline zwitterion.

General procedure: L-Proline(2.0 g, 17.4 mmol) was dissolved in methanol (20 mL) and40 percent aqueous formaldehyde (1.4 mL, 19.1 mmol) wasadded to this solution. Next, 10 percent Pd/C catalyst (500 mg)was added to the reaction mixture and the resulting slurrywas stirred in hydrogen overnight. The slurry was then filtered through a Celite pad to remove the catalyst. Thepad was washed with methanol and the combined filtrateswere concentrated under reduced pressure. The residue wasdissolved in ethanol/benzene (1:1, 100 mL) and concentratedsecond time to provide a solid that was re-crystallizedin methanol/diethyl ether. In this way Nmethylproline7a was isolated as fine needles (2.1 g, 92 percentyield); mp 109–111°C; 1H NMR (D2O, 300 MHz):δ = 3.95–3.90 (1H, m, CH2 (CH2)2CHNCH3), 3.24–3.15(2H, m, CH2 (CH2)2CHNCH3), 2.97 (3H, s, CH2 (CH2)2CHNCH3), 2.22–2.01 (4H, m, CH2 (CH2)2CHNCH3); ESI–MS (m/z):130.2 [M + H] +(100).L-proline (4.0 g, 34.8 mmol)Soluble in methanol (40mL), 40percent aqueous formaldehyde solution (2.8 mL, 38.2 mmol) was added in orderAnd 10percent Pd on carbon (1g), addition, hydrogenation, Reaction at room temperature for 24 hours, After the reaction is complete, filterThe mother liquor was concentrated and dried to give 4g of a white solid with a yield of 89percent.That is, N-methyl-L-proline (compound b).The vigorously stirred suspension of zinc dust(6.50 g; 100 mmol), L-proline (5.57 g; 50 mmol) and NaH2PO4 (11.90 g; 100 mmol) in water (22 mL) was treated with 35percent aq. formaldehyde (2.10 mL).Stirring was continued for 48 h at 30°C. The suspension was discarded, the filtrate was neutralized with2 M aq. ammonia to pH 8, concentrated under vacuum, the solid residue was dissolved in small amount of water and lyophilized. Dry residue was extracted with hot mixture of benzene-ethanol (1 : 1, v/v).Collected extracts were evaporated to dryness and then recrystallized from the mixture methanol/ether affording L-N-methylproline (1) (5.68 g; yield 88percent)as white crystals m.p. 115-120°C, lit. (12) m.p.115-116°C.3a. 3a. 3 a. N-Methyl (L)-proline General procedure: L-Proline(2.0 g, 17.4 mmol) was dissolved in methanol (20 mL) and40 % aqueous formaldehyde (1.4 mL, 19.1 mmol) wasadded to this solution. Next, 10 % Pd/C catalyst (500 mg)was added to the reaction mixture and the resulting slurrywas stirred in hydrogen overnight. The slurry was then filtered through a Celite pad to remove the catalyst. Thepad was washed with methanol and the combined filtrateswere concentrated under reduced pressure. The residue wasdissolved in ethanol/benzene (1:1, 100 mL) and concentratedsecond time to provide a solid that was re-crystallizedin methanol/diethyl ether. In this way Nmethylproline7a was isolated as fine needles (2.1 g, 92 %yield); mp 109-111C; 1H NMR (D2O, 300 MHz):delta = 3.95-3.90 (1H, m, CH2 (CH2)2CHNCH3), 3.24-3.15(2H, m, CH2 (CH2)2CHNCH3), 2.97 (3H, s, CH2 (CH2)2CHNCH3), 2.22-2.01 (4H, m, CH2 (CH2)2CHNCH3); ESI-MS (m/z):130.2 [M + H] +(100).L-proline (4.0 g, 34.8 mmol)Soluble in methanol (40mL), 40% aqueous formaldehyde solution (2.8 mL, 38.2 mmol) was added in orderAnd 10% Pd on carbon (1g), addition, hydrogenation, Reaction at room temperature for 24 hours, After the reaction is complete, filterThe mother liquor was concentrated and dried to give 4g of a white solid with a yield of 89%.That is, The vigorously stirred suspension of zinc dust(6.50 g; 100 mmol), L-proline (5.57 g; 50 mmol) and NaH2PO4 (11.90 g; 100 mmol) in water (22 mL) was treated with 35% aq. formaldehyde (2.10 mL).Stirring was continued for 48 h at 30C. The suspension was discarded, the filtrate was neutralized with2 M aq. ammonia to pH 8, concentrated under vacuum, the solid residue was dissolved in small amount of water and lyophilized. Dry residue was extracted with hot mixture of benzene-ethanol (1 : 1, v/v).Collected extracts were evaporated to dryness and then recrystallized from the mixture methanol/ether affording L-N-methylproline (1) (5.68 g; yield 88%)as white crystals m.p. 115-120C, lit. (12) m.p.115-116C.

Molecular Weight:129.16
XLogP3:-1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:129.078978594
Monoisotopic Mass:129.078978594
Topological Polar Surface Area:40.5
Heavy Atom Count:9
Complexity:124
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes