3-Fluoro-4-methylbenzylamine → Racemic-trans-n-(2-{[(3-fluoro-4-methylbenzyl)amino]carbonyl}-3-hydroxy-6-methyl-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)-n,n',n'-trimethylethanediamide

HRID 1893202Notes

Reaction equation

[CH3:1][N:2]([C:4](=[O:31])[C:5]([N:7]([CH3:30])[C@@H:8]1[CH2:14][CH2:13][CH2:12][C@@H:11]([CH3:15])[N:10]2[C:16](=[O:29])[C:17]([O:24]S(C)(=O)=O)=[C:18]([C:20](OC)=[O:21])[N:19]=[C:9]12)=[O:6])[CH3:3].[CH3:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH2:38])=[CH:35][C:34]=1[F:41]>CS(C)=O>[F:41][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][C:33]=1[CH3:32])[CH2:37][NH:38][C:20]([C:18]1[N:19]=[C:9]2[C@H:8]([N:7]([CH3:30])[C:5](=[O:6])[C:4]([N:2]([CH3:3])[CH3:1])=[O:31])[CH2:14][CH2:13][CH2:12][C@@H:11]([CH3:15])[N:10]2[C:16](=[O:29])[C:17]=1[OH:24])=[O:21]

Participants

Conditions

Temperature: 100 °C

Procedure

The trans-rac-methyl 10-[[(dimethylamino)(oxo)acetyl](methyl)amino]-6-methyl-3-[(methylsulfonyl)oxy]-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepine-2-carboxylate from Step 10 (50 mg) was dissolved in DMSO (2 mL) and 4-methyl-3-fluorobenzylamine (0.1 mL) added. The resulting mixture was heated at 100° C. for 30 minutes. As determined by LC-MS, there was complete conversion to product which was purified by reverse phase Gilson chromatography: 1H NMR (400 MHz, CDCl3) δ 9.46 (br s, 1H), 7.05 (m, 3H), 5.96 (m, 1H), 5.56 (br s, 1H), 4.47 (qd, J=6.8, 14.5 Hz, 2H), 3.02 (s, 3H), 2.99 (s, 3H), 2.94 (s, 3H), 2.21 (s, 3H), 1.61-2.24 (m, 6H), 1.47 (d, J=7.5 Hz, 3H). ES MS M+1=487.8.

Workup

customwas purified by reverse phase Gilson chromatography

Sources & evidence

ORD record: ord-723bcfc8618b47139502242504f97bc1
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513234B2

Reaction notes

Loading…