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]propane-2-sulfonamide

HRID 601400Notes

Reaction equation

HRID 601400 reaction equation
[NH2:1][CH2:2][C:3]1[C:11]2[S:10](=[O:13])(=[O:12])[N:9]=[C:8]([C:14]3[C:15](=[O:30])[N:16]([NH:25][CH2:26][CH:27]4[CH2:29][CH2:28]4)[C:17]4[C:22]([C:23]=3[OH:24])=[CH:21][CH:20]=[CH:19][CH:18]=4)[NH:7][C:6]=2[S:5][CH:4]=1.C(N(CC)CC)C.[CH:38]([S:41](Cl)(=[O:43])=[O:42])([CH3:40])[CH3:39]>CN(C)C=O>[CH:27]1([CH2:26][NH:25][N:16]2[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:23]([OH:24])=[C:14]([C:8]3[NH:7][C:6]4[S:5][CH:4]=[C:3]([CH2:2][NH:1][S:41]([CH:38]([CH3:40])[CH3:39])(=[O:43])=[O:42])[C:11]=4[S:10](=[O:12])(=[O:13])[N:9]=3)[C:15]2=[O:30])[CH2:28][CH2:29]1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 824082-Propanesulfonyl chloride3×HCID 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 136358513N-[(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]propane-2-sulfonamideYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the product of Example 353E (16.2 mg, 0.036 mmol) in N,N-dimethylformamide (0.4 mL) was added triethylamine (0.011 mL, 0.079 mmol). The mixture was cooled to 0° C. and isopropyl sulfonyl chloride was added (0.0043 mL, 0.038 mmol). The mixture was warmed to 23° C. and stirred for 3 hours. Additional isopropyl sulfonyl chloride (0.006 mL, 0.055 mmol) was added and the reaction mixture was stirred at 23° C. for 15 hours. The reaction mixture was stirred at 50° C. for 2 hours. Additional triethylamine (0.040 mL, 0.287 mmol) and isopropyl sulfonyl chloride (0.010 mL, 0.091 mmol) were added and the reaction mixture was stirred at 50° C. for 2 hours. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was purified by reverse phase chromatography, eluting with a gradient of 10% acetonitrile/0.1% trifluoroacetic acid in water to 95% acetonitrile/0.1% trifluoracetic acid in water to give the title compound (6.7 mg, 33%). The sodium salt of the title compound was prepared according to the procedure of Example 1D. 1H NMR (300 MHz, DMSO-d6) δ 0.21 (bs, 2 H) 0.48 (d, 2 H) 0.98 (m, 1 H) 1.24 (d, J=6.99 Hz, 6 H) 3.19 (m, 1 H) 4.25 (s, 2 H) 5.85 (t, 1 H) 6.76 (s, 1 H) 6.92 (t, 1 H) 7.34 (m, 2 H) 7.57 (d, 1 H) 7.96 (d, 1 H).

Workup

  1. temperatureThe mixture was warmed to 23° C.
  2. stirringthe reaction mixture was stirred at 23° C. for 15 hours
  3. stirringThe reaction mixture was stirred at 50° C. for 2 hours
  4. stirringthe reaction mixture was stirred at 50° C. for 2 hours
  5. temperatureThe reaction mixture was cooled to 25° C.
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by reverse phase chromatography
  8. washeluting with a gradient of 10% acetonitrile/0.1% trifluoroacetic acid in water to 95% acetonitrile/0.1% trifluoracetic acid in water

Sources & evidence

ORD record
ord-bc795d5e049549549d94fecbcb945204
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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