Methanesulfonyl chloride → N-{2-[(3-{1-[(cyclopropylmethyl)amino]-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl}-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl)oxy]ethyl}methanesulfonamide

HRID 601372Notes

Reaction equation

HRID 601372 reaction equation
[NH2:1][CH2:2][CH2:3][O:4][C:5]1[CH:33]=[CH:32][C:8]2[NH:9][C:10]([C:15]3[C:16](=[O:31])[N:17]([NH:26][CH2:27][CH:28]4[CH2:30][CH2:29]4)[C:18]4[C:23]([C:24]=3[OH:25])=[CH:22][CH:21]=[CH:20][CH:19]=4)=[N:11][S:12](=[O:14])(=[O:13])[C:7]=2[CH:6]=1.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>N1C=CC=CC=1>[CH:28]1([CH2:27][NH:26][N:17]2[C:18]3[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:24]([OH:25])=[C:15]([C:10]3[NH:9][C:8]4[CH:32]=[CH:33][C:5]([O:4][CH2:3][CH2:2][NH:1][S:35]([CH3:34])(=[O:37])=[O:36])=[CH:6][C:7]=4[S:12](=[O:14])(=[O:13])[N:11]=3)[C:16]2=[O:31])[CH2:30][CH2:29]1

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 1363584273-[7-(2-aminoethoxy)-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl]-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one

Product 1

HCID 136358428N-{2-[(3-{1-[(cyclopropylmethyl)amino]-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl}-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl)oxy]ethyl}methanesulfonamideYield 29%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
120 °C

Procedure

To the product of Example 394 (15 mg, 0.032 mmol) in pyridine (1 mL) was added methanesulfonyl chloride (12 μl, 0.156 mmol). The reaction mixture was heated in a microwave reactor at 120° C. for 120 minutes. The reaction was cooled to 25° C. and concentrated under reduced pressure. The residue was triturated with water (1 mL), filtered, and washed with 1:1 hexane:ethyl acetate. The crude product was purified by chromatography on silica gel eluting with 199:1 dichloromethane:methanol to give the title compound (5 mg, 29%). 1H NMR (300 MHz, DMSO-d6) δ 0.14 (d, J=4.04 Hz, 2 H) 0.41 (d, J=7.72 Hz, 2 H) 1.01 (m, 1 H) 2.86 (d, J=5.52 Hz, 2 H) 2.97 (s, 3 H) 3.38 (t, J=5.33 Hz, 2 H) 4.18 (t, J=5.33 Hz, 2 H) 6.44 (s, 1 H) 7.32 (t, J=5.88 Hz, 1 H) 7.41 (m, 3 H) 7.67 (d, J=9.93 Hz, 1 H) 7.89 (t, J=7.91 Hz, 1 H) 8.10 (d, J=8.46 Hz, 1 H) 8.17 (d, J=8.46 Hz, 1 H) 14.08 (s, 1 H) 15.11 (s, 1 H). MS (ESI−) m/z 546 (M−H)−.

Workup

  1. temperatureThe reaction was cooled to 25° C.
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was triturated with water (1 mL)
  4. filtrationfiltered
  5. washwashed with 1:1 hexane
  6. customThe crude product was purified by chromatography on silica gel eluting with 199:1 dichloromethane

Sources & evidence

ORD record
ord-cf962a7cfadf47ae960a7e7d417b7b42
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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