Triethylamine → Ethyl 3-(benzyloxy)-9-(2-(methylthio)ethyl)-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate

HRID 1726543Notes

Reaction equation

HRID 1726543 reaction equation
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[NH:13][C:12]([CH:16]([O:21][CH2:22][CH2:23]O)[CH2:17][CH2:18][S:19][CH3:20])=[N:11][C:10]=1[C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.CS(Cl)(=O)=O>C(Cl)Cl.CCOCC>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]2[C:12]([CH:16]([CH2:17][CH2:18][S:19][CH3:20])[O:21][CH2:22][CH2:23]2)=[N:11][C:10]=1[C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 135848642Ethyl 5-(benzyloxy)-2-(1-(2-hydroxyethoxy)-3-(methylthio)propyl)-6-oxo-1,6-dihydropyrimidine-4-carboxylate

Product 1

HCID 21069951Ethyl 3-(benzyloxy)-9-(2-(methylthio)ethyl)-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylateYield 52.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of intermediate 20, ethyl 5-(benzyloxy)-2-(1-(2-hydroxyethoxy)-3-(methylthio)propyl)-6-oxo-1,6-dihydropyrimidine-4-carboxylate, (527 mg, 1.25 mmol) and Et3N (505 mg, 5 mmol) dissolved in 10 mL of CH2Cl2 was added a solution of CH3SO2Cl (288 mg, 2.5 mmol) dissolved in 2 mL of CH2Cl2. This was stirred for 20 hrs then concentrated. The crude product was purified by chromatography on silica gel, using 10:1 CH2Cl2:ether as eluent, to give the title compound 265 mg (52% yield). (500 MHz, CDCl3) δ ppm: 7.31-7.55 (5H, m) 5.30 (2H, s) 4.75 (1H, dd, J=3.66 Hz) 4.32-4.40 (2H, q, J=7.17 Hz) 4.13-4.30 (2H, m) 3.75-3.97 (2H, m) 2.20-2.84 (4H, m) 2.06 (3H, s) 1.32 (3H, t, J=7.17 Hz); LC/MS m/z 405 (M+H).

Workup

  1. concentrationthen concentrated
  2. customThe crude product was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-c5f3e1c7ce6244e5a9509822435243bc
Source dataset
uspto-grants-2009_02
Patent number
US07491819B1

Reaction notes

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