Formic Acid → HCID 25101612, compound

HRID 336811Notes

Reaction equation

HRID 336811 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[NH:10][C:11]1[C:12]([NH:21][S:22]([C:25]2[CH:26]=[C:27]([CH:38]=[CH:39][CH:40]=2)[C:28]([NH:30][CH2:31][CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][NH:33]2)=[O:29])(=[O:24])=[O:23])=[N:13][C:14]2[C:19]([N:20]=1)=[CH:18][CH:17]=[CH:16][CH:15]=2.[CH:41](O)=O.C=O>CC(N(C)C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[NH:10][C:11]1[C:12]([NH:21][S:22]([C:25]2[CH:26]=[C:27]([CH:38]=[CH:39][CH:40]=2)[C:28]([NH:30][CH2:31][CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][N:33]2[CH3:41])=[O:29])(=[O:24])=[O:23])=[N:13][C:14]2[C:19]([N:20]=1)=[CH:18][CH:17]=[CH:16][CH:15]=2

Participants

5

Reactant 3

HCID 284Formic AcidHCID 712FormaldehydeHCID 25101309HCID 25101309, compound

Product 1

HCID 25101612HCID 25101612, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-2-ylmethyl)benzamide (299 mg, 0.51 mmol, 1 equiv), prepared using procedures similar to those described for Example 514, was dissolved in 2.3 mL of DMA. Formic acid (388 μL, 10.28 mmol, 20 equiv) was added to solution with stirring followed by the addition of formaldehyde (508 μL of 37% aq. solution). The reaction was then stirred at room temperature overnight. Analysis of an aliquot of the reaction mixture by LCMS indicated the complete consumption of starting material. The reaction was diluted with methanol (2 mL). Preparative reverse-phase HPLC was used to isolate the desired product directly from the crude reaction mixture. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 μM, 30×70 mm column and running a 5-100% gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. 1H NMR (400 MHz, d6-DMSO): 9.44 (s, 1H), 8.94 (s, 1H), 8.79 (t, 1H), 8.57 (s, 1H), 8.27 (d, 1H), 7.90 (d, 1H) 7.54 (t, 1H), 7.46 (d, 1H), 7.39 (d, 1H), 7.33 (d, 1H), 7.18 (m, 2H), 6.60 (dd, 1H), 3.82 (s, 3H), 3.59 (m, 2H), 3.00 (s, 1H), 2.90 (s, 3H), 1.62 (m, 7H); MS (EI) m/z for C29H31ClN6O4S: 595 (MH+).

Workup

  1. stirringThe reaction was then stirred at room temperature overnight
  2. customthe complete consumption of starting material
  3. additionThe reaction was diluted with methanol (2 mL)

Sources & evidence

ORD record
ord-92befd1fdbd14be695ad7e174bd3c2bd
Source dataset
uspto-grants-2014_11
Patent number
US08889664B2

Reaction notes

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