Phosphate → HCID 58964514, compound

HRID 2069309Notes

Reaction equation

HRID 2069309 reaction equation
[CH3:1][S:2]([NH:5][N:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][C:11]([C:27]([F:30])([F:29])[F:28])=[C:12]([N:17]3[CH:21]=[CH:20][C:19]([CH2:22][O:23]C(=O)C)=[CH:18]3)[CH:13]=2)[NH:8][C:7]1=[O:31])(=[O:4])=[O:3].C(=O)([O-])[O-].[K+].[K+].P([O-])([O-])([O-])=O>CO>[OH:23][CH2:22][C:19]1[CH:20]=[CH:21][N:17]([C:12]2[CH:13]=[C:14]3[C:9](=[CH:10][C:11]=2[C:27]([F:29])([F:28])[F:30])[NH:8][C:7](=[O:31])[N:6]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])[C:15]3=[O:16])[CH:18]=1

Participants

5

Reactant 3

HCID 1061PhosphateHCID 11430Potassium CarbonateHCID 58964505HCID 58964505, compound

Product 1

HCID 58964514HCID 58964514, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 100 mg (0.22 mmol) of acetic acid 1-(3-methanesulfonylamino-2,4-dioxo-7 -trifluoromethyl-1,2,3,4-tetrahydro-quinazolin-6-yl)-1H-pyrrol-3-ylmethyl ester in 0.5 ml of methanol are added 36.4 mg (0.26 mmol) of potassium carbonate and the reaction mixture is stirred at 55° C. for 8 hours. The mixture is cooled to room temperature and stirred for another 12 hours. Subsequently a pH 7 phosphate buffer solution for neutralization is added to the reaction mixture and the solvents are evaporated carefully (risk of degradation). The crude residue is purified by preparative thin layer chromatography (dichloromethane/methanol, 8/2) to yield N-[6-(3-hydroxymethyl-pyrrol-1-yl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide: 1H-NMR; DMSO-d6 (400 MHz, ppm): 7.82 (s, 1H , aromatic); 7.64 (s, 1H , aromatic); 6.86 (m, 1H, N-CH═CH in pyrrol); 6.84 (s, 1H, N-CH═C(CH2) in pyrrol); 6.21 (m, 1H, CH═CH-C(CH2)-N in pyrrol); 4.37 (d, 2H, CH2-OH); 3.16 (s, 3H, S02-CH3); LC-MS: 417 [M-H]-; Agilent LC/MSD 1100 Series, LC-MS method: Column: SunFireC18, 4.6*50 mm, 3.5 μm; negative MS; water/acetonitril 95:5 to 5:95 in 5 min, flow: 1.5 ml/min.

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. stirringstirred for another 12 hours
  3. customthe solvents are evaporated carefully (risk of degradation)
  4. customThe crude residue is purified by preparative thin layer chromatography (dichloromethane/methanol, 8/2)

Sources & evidence

ORD record
ord-f7441c6c4de1496f9a6730065b221ccb
Source dataset
uspto-grants-2012_10
Patent number
US08299085B2

Reaction notes

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