Formic Acid → Dimethylcarbamic acid 3-(3-aminosulfonylamino-2-fluoro-benzyl)-4-fluoromethyl-2-oxo-2H-1-benzopyran-7-yl ester

HRID 2061116Notes

Reaction equation

HRID 2061116 reaction equation
Cl[S:2]([N:5]=C=O)(=[O:4])=[O:3].C(O)=O.[NH2:11][C:12]1[C:13]([F:38])=[C:14]([CH:35]=[CH:36][CH:37]=1)[CH2:15][C:16]1[C:17](=[O:34])[O:18][C:19]2[CH:27]=[C:26]([O:28][C:29](=[O:33])[N:30]([CH3:32])[CH3:31])[CH:25]=[CH:24][C:20]=2[C:21]=1[CH2:22][F:23].C(=O)([O-])O.[Na+]>ClCCl.N1C=CC=CC=1>[NH2:5][S:2]([NH:11][C:12]1[C:13]([F:38])=[C:14]([CH:35]=[CH:36][CH:37]=1)[CH2:15][C:16]1[C:17](=[O:34])[O:18][C:19]2[CH:27]=[C:26]([O:28][C:29](=[O:33])[N:30]([CH3:32])[CH3:31])[CH:25]=[CH:24][C:20]=2[C:21]=1[CH2:22][F:23])(=[O:4])=[O:3]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 70918Chlorosulfonyl isocyanateHCID 516892Sodium BicarbonateHCID 59139194Dimethylcarbamic acid 3-(3-amino-2-fluorobenzyl)-4-fluoromethyl-2-oxo-2H-1-benzopyran-7-yl ester

Product 1

HCID 24753503Dimethylcarbamic acid 3-(3-aminosulfonylamino-2-fluoro-benzyl)-4-fluoromethyl-2-oxo-2H-1-benzopyran-7-yl ester

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

Chlorosulfonyl isocyanate (0.150 mL) and formic acid (0.065 mL) were mixed at 0° C., and the mixture was stirred at room temperature for 1 hour. Dichloromethane (1.2 mL) was added to this mixture and dissolved, and the mixture was further stirred at room temperature for 4 hours. 0.060 mL was taken from the solution, and added at 0° C. to a solution of dimethylcarbamic acid 3-(3-amino-2-fluorobenzyl)-4-fluoromethyl-2-oxo-2H-1-benzopyran-7-yl ester (compound 1h-1-4F) (25.2 mg) in dichloromethane (1.0 mL)/pyridine (0.0065 mL), and the mixture was stirred at room temperature for 3 hours. Saturated sodium hydrogen carbonate was then added to the reaction solution, and the mixture was extracted with ethyl acetate, The extracted liquid was washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure, and the resultant residue was purified by thin layer silica gel chromatography (aminogel) (dichloromethane:methanol=90:10) to yield the title compound (12.0 mg).

Workup

  1. dissolutiondissolved
  2. stirringthe mixture was further stirred at room temperature for 4 hours
  3. stirringthe mixture was stirred at room temperature for 3 hours
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extracted liquid was washed with saturated saline
  6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  7. distillationThe solvent was distilled away under reduced pressure
  8. customthe resultant residue was purified by thin layer silica gel chromatography (aminogel) (dichloromethane:methanol=90:10)

Sources & evidence

ORD record
ord-093050de6d9c420893c2c3495a618dd6
Source dataset
uspto-grants-2012_10
Patent number
US08278465B2

Reaction notes

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