Triethylamine → N-[(3-{1-[(cyclopropylmethyl)amino]-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl}-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-7-yl)methyl]methanesulfonamide

HRID 552104Notes

Reaction equation

HRID 552104 reaction equation
C(N(CC)CC)C.[NH2:8][CH2:9][C:10]1[C:18]2[S:17](=[O:20])(=[O:19])[N:16]=[C:15]([C:21]3[C:22](=[O:37])[N:23]([NH:32][CH2:33][CH:34]4[CH2:36][CH2:35]4)[C:24]4[C:29]([C:30]=3[OH:31])=[CH:28][CH:27]=[CH:26][CH:25]=4)[NH:14][C:13]=2[S:12][CH:11]=1.[CH3:38][S:39](Cl)(=[O:41])=[O:40]>CN(C)C=O>[CH:34]1([CH2:33][NH:32][N:23]2[C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:30]([OH:31])=[C:21]([C:15]3[NH:14][C:13]4[S:12][CH:11]=[C:10]([CH2:9][NH:8][S:39]([CH3:38])(=[O:41])=[O:40])[C:18]=4[S:17](=[O:19])(=[O:20])[N:16]=3)[C:22]2=[O:37])[CH2:35][CH2:36]1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chlorideHCID 1363584943-[7-(aminomethyl)-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one

Product 1

HCID 136347190N-[(3-{1-[(cyclopropylmethyl)amino]-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl}-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-7-yl)methyl]methanesulfonamideYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the suspension of the triethylamine salt of 3-[7-(aminomethyl)-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one (85.26 mg, 0.16 mmol) in N,N-dimethylformamide (1.6 mL) was added triethylamine (48 □L, 0.34 mmol) and then methanesulfonyl chloride (13.3 □L, 0.17 mmol) at room temperature. The solution was stirred at room temperature for 20 minutes and concentrated in vacuo. The residue purified by reverse phase chromatography, eluting with 20% to 95% acetonitrile/0.1% trifluoroacetic acid in water to give N-[(3-{1-[(cyclopropylmethyl)amino]-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl}-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-7-yl)methyl]methanesulfonamide (compound II) (39.86 mg, 49%). MS (ESI+) m/z 524 (M+H)+. NMR (300 MHz, DMSO-d6) δ 0.15 (m, 2 H) 0.42 (m, 2 H) 1.01 (m, 1 H) 2.84 (d, J=7.35 Hz, 2 H) 2.99 (s, 3 H) 4.29 (d, J=6.25 Hz, 2 H) 6.37 (br s, 1 H) 7.41 (m, 2 H) 7.75 (t, J=6.25 Hz, 1 H) 7.87 (m, 1 H) 8.08 (d, J=8.09 Hz, 1 H) 8.16 (m, 1 H) 14.46 (m, 1 H).

Workup

  1. customat room temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue purified by reverse phase chromatography
  4. washeluting with 20% to 95% acetonitrile/0.1% trifluoroacetic acid in water

Sources & evidence

ORD record
ord-253eec8cb65b4b35927b0c78fd9ea788
Source dataset
uspto-grants-2011_05
Patent number
US07951800B2

Reaction notes

Loading…