Formic Acid → HCID 25101612, compound

HRID 237371Notes

Reaction equation

HRID 237371 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

A measured amount of 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-2-ylmethyl)benzamide (299 mg, 0.51 mmol, 1 eq) was dissolved in 2.3 mL of DMA. Formic acid (388 ul, 10.28 mmol, 20 eq) was added to solution with stirring followed by the addition of formaldehyde (508 ul 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 □M, 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) 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-62dd9de819b842038c33f947924c0b2f
Source dataset
uspto-grants-2014_02
Patent number
US08642584B2

Reaction notes

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