Acetonitrile → n-[4-(2,4-Dioxo(1,3-dihydroquinazolin-3-yl))phenyl]{[(5-chloro-3-fluoro(2-thienyl))sulfonyl]amino}carboxamide

HRID 38169

Reaction equation

HRID 38169 reaction equation
[C:1]([NH:5][S:6]([C:9]1[S:10][C:11]([Cl:15])=[CH:12][C:13]=1[F:14])(=[O:8])=[O:7])(C)(C)C.C1CCN2C(=NCCC2)CC1.FC(F)(F)C(O)=[O:30].[NH2:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]2[C:50](=[O:51])[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[NH:43][C:42]2=[O:52])=[CH:37][CH:36]=1.C(#N)C>C(O)(C(F)(F)F)=O>[O:52]=[C:42]1[N:41]([C:38]2[CH:39]=[CH:40][C:35]([NH:34][C:1]([NH:5][S:6]([C:9]3[S:10][C:11]([Cl:15])=[CH:12][C:13]=3[F:14])(=[O:8])=[O:7])=[O:30])=[CH:36][CH:37]=2)[C:50](=[O:51])[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[NH:43]1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 220643913-(4-Aminophenyl)-1,3-dihydroquinazoline-2,4-dione trifluoroacetateHCID 22064462(Tert-butyl)[(5-chloro-3-fluoro(2-thienyl))sulfonyl]amine

Product 1

HCID 22064426n-[4-(2,4-Dioxo(1,3-dihydroquinazolin-3-yl))phenyl]{[(5-chloro-3-fluoro(2-thienyl))sulfonyl]amino}carboxamideYield 34%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A 19 mg-sample (0.07 mmol) of (tert-butyl)[(5-chloro-3-fluoro(2-thienyl))sulfonyl]amine was dissolved in neat TFA and stirred for 1 h, concentrated in vacuo and used directly in the next transformation. This sample was dissolved in 150 uL of DCM and 21 mg (0.084 mmol) of DSC was added followed by 21 μL (0.14 mmol) of DBU. This solution was stirred for 18 h, 26 mg (0.07) of 3-(4-aminophenyl)-1,3-dihydroquinazoline-2,4-dione trifluoroacetate salt was added plus 150 μL of dry acetonitrile and refluxed for 2 h. This material was then purified on RP-HPLC to afford 11 mg (34%) of the desired product. BS-MS: M+H+=495 (Cl).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThis sample was dissolved in 150 uL of DCM
  3. addition21 mg (0.084 mmol) of DSC was added
  4. stirringThis solution was stirred for 18 h
  5. temperaturerefluxed for 2 h
  6. customThis material was then purified on RP-HPLC

Sources & evidence

ORD record
ord-c402dd8d3437460b920d5e0d79eff05a
Source dataset
uspto-grants-2013_09
Patent number
US08524721B2

Linked notes

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