Dimethylformamide → HCID 58328258, compound

HRID 544950Notes

Reaction equation

HRID 544950 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:26])=[C:11]([NH:13][C:14]([C:16]3[CH:24]=[C:23]4[C:19]([CH:20]=[CH:21][N:22]4[CH3:25])=[CH:18][CH:17]=3)=[O:15])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1.ClS([N:31]=[C:32]=O)(=O)=O.CN(C=O)C>C(#N)C>[C:32]([C:20]1[C:19]2[C:23](=[CH:24][C:16]([C:14]([NH:13][C:11]3[CH:12]=[C:7]([C:5](=[O:6])[NH:4][CH:1]4[CH2:2][CH2:3]4)[CH:8]=[CH:9][C:10]=3[CH3:26])=[O:15])=[CH:17][CH:18]=2)[N:22]([CH3:25])[CH:21]=1)#[N:31]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 70918Chlorosulfonyl isocyanateHCID 58328191HCID 58328191, compound

Product 1

HCID 58328258HCID 58328258, compoundYield 10.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-1-methyl-1H-indole-6-carboxamide (0.045 g, 0.129 mmol, example 97, table 5) in anhydrous acetonitrile (2 mL) was added chlorosulfonyl isocyanate (11 μL, 0.129 mmol) at room temperature. The reaction mixture was stirred at room temperature for 30 min. and DMF (11 μL, 0.141 mmol) is added. After another 30 min. at room temperature, the reaction mixture was quenched with methanol (2 mL), concentrated under reduced pressure and subjected to reverse phase preparative HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA). The desired fractions were collected, and concentrated using speedVac® Plus (SC250DDA) to yield the title compound (Example 223, 0.005 g). HPLC retention time (YMC S5 Combiscreen ODS; 4.6×50 mm (4 min. gradient); Solvent A=10% MeOH, 90% H2O, 0.2% H3PO4; solvent B=90% MeOH, 10% H2O, 0.2% H3PO4): 2.6 min. LCMS [M+H]+ 373.2.

Workup

  1. waitAfter another 30 min. at room temperature
  2. customthe reaction mixture was quenched with methanol (2 mL)
  3. concentrationconcentrated under reduced pressure
  4. customphase preparative HPLC (YMC S5 20×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA)
  5. customThe desired fractions were collected
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-22cc8b1751474d82a94f697893edfdc8
Source dataset
uspto-grants-2011_05
Patent number
US07935696B2

Reaction notes

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