1-Propanesulfonyl chloride → HCID 136358509, compound

HRID 601389Notes

Reaction equation

HRID 601389 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:28])[N:14]([CH2:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C:15]4[C:20]([C:21]=3[OH:22])=[CH:19][CH:18]=[CH:17][N:16]=4)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.[CH2:31]([S:34](Cl)(=[O:36])=[O:35])[CH2:32][CH3:33]>N1C=CC=CC=1>[OH:22][C:21]1[C:20]2[C:15](=[N:16][CH:17]=[CH:18][CH:19]=2)[N:14]([CH2:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C:13](=[O:28])[C:12]=1[C:7]1[NH:6][C:5]2[CH:29]=[CH:30][C:2]([NH:1][S:34]([CH2:31][CH2:32][CH3:33])(=[O:36])=[O:35])=[CH:3][C:4]=2[S:9](=[O:11])(=[O:10])[N:8]=1

Participants

4

Reactant 2

HCID 662791-Propanesulfonyl chlorideHCID 1354307103-(7-Amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-(3-methylbutyl)-1,8-naphthyridin-2(1H)-one

Product 1

HCID 136358509HCID 136358509, compoundYield 11.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
120 °C

Procedure

To the product of Example 205 (21.5 g, 0.05 mmol) in pyridine (1 mL) was added 1-propanesulfonyl chloride (22.5 mL, 0.2 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 chromatographed on reverse phase HPLC eluting with 0.1% aqueous trifluoroacetic acid/methanol (90/10) to 0.1% aqueous trifluoroacetic acid/methanol (5/95) to give the title compound (3 mg, 11%). 1H NMR (300 MHz, DMSO-d6) δ 0.97 (m, 9 H) 1.57 (m, 2 H) 1.69 (m, 3 H) 3.17 (t, J=7.74 Hz, 2 H) 4.49 (t, J=7.74 Hz, 2 H) 7.50 (dd, J=7.91, 4.60 Hz, 1 H) 7.58 (dd, J=8.82, 2.57 Hz, 1 H) 7.64 (d, J=2.21 Hz, 1 H) 7.75 (d, J=8.82 Hz, 1 H) 8.56 (dd, J=7.72, 1.84 Hz, 1 H) 8.90 (dd, J=4.41, 1.84 Hz, 1 H) 10.35 (s, 1 H) 14.09 (s, 1 H). MS (ESI−) m/z 532 (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 chromatographed on reverse phase HPLC
  7. washeluting with 0.1% aqueous trifluoroacetic acid/methanol (90/10) to 0.1% aqueous trifluoroacetic acid/methanol (5/95)

Sources & evidence

ORD record
ord-c6ace9d967a24deb89b3dde5c0301c0a
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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