Phosgene → 2-methyl-N-(4-oxo-4H-1-benzopyran-3-yl)-4-(1-pyrrolidinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide

HRID 2057889Notes

Reaction equation

[C:1](Cl)(Cl)=[O:2].[CH3:5][N:6]1[CH:11]=[C:10]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[C:9]2[CH:17]=[CH:18][CH:19]=[CH:20][C:8]=2[S:7]1(=[O:22])=[O:21].C(N(CC)CC)C.[NH2:30][C:31]1[C:36](=[O:37])[C:35]2[CH:38]=[CH:39][CH:40]=[CH:41][C:34]=2[O:33][CH:32]=1>C1(C)C=CC=CC=1.O1CCCC1>[CH3:5][N:6]1[C:11]([C:1]([NH:30][C:31]2[C:36](=[O:37])[C:35]3[CH:38]=[CH:39][CH:40]=[CH:41][C:34]=3[O:33][CH:32]=2)=[O:2])=[C:10]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[C:9]2[CH:17]=[CH:18][CH:19]=[CH:20][C:8]=2[S:7]1(=[O:22])=[O:21]

Participants

Conditions

Temperature: -40 °C

Procedure

A solution of 2.5 g (0.025 mole) of phosgene in toluene is diluted with 50 ml of dry tetrahydrofurane and then cooled to a temperature of -40° C. A solution of 6.6 g (0.025 mole) of 2-methyl-4-(1-pyrrolidinyl)-2H-1,2-benzothiazine 1,1-dioxide and 2.5 g (0.025 mole) of triethylamine in 200 ml of tetrahydrofurane is then added slowly, with stirring, at a temperature of -40° to +55° C. in the course of 30 minutes. The reaction mixture is stirred for 12 hours at room temperature, then cooled to 10° C., and subsequently a suspension of 6.25 g (0.05 mole) of 3-amino-4-oxo-4H-1-benzopyrane in 100 ml of tetrahydrofurane is added slowly. The temperature of the reaction mixture is allowed to rise to room temperature. The reaction mixture is then stirred for 72 hours and poured into ice-water. The precipitate is collected by suction and crystallised from tetrahydrofurane, affording pure crystalline 2-methyl-N-(4-oxo-4H-1-benzopyran-3-yl)-4-(1-pyrrolidinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide. 2-Methyl-3,4-dihydro-4-oxo-N-(6-chloro-7-methyl-4-oxo-4H-1-benzopyran-3-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide can be obtained in analogeous manner starting from 2-methyl-N-(6-chloro-7-methyl-4-oxo.4H-1 -benzopyran-3-yl)-4-(1-pyrrolidinyl)-1,2-benzothiazine-3-carboxamide 1,1-dioxide.

Workup

stirringThe reaction mixture is stirred for 12 hours at room temperature
temperaturecooled to 10° C.
additionis added slowly
customto rise to room temperature
stirringThe reaction mixture is then stirred for 72 hours
customThe precipitate is collected by suction
customcrystallised from tetrahydrofurane

Sources & evidence

ORD record: ord-b886ba364b9b424c9ac4de2e3767cc47
Source dataset: uspto-grants-1980_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04213980

Reaction notes

Loading…