Benzenesulfonyl chloride → HCID 67425880, compound

HRID 2383452Notes

Reaction equation

HRID 2383452 reaction equation
OC(C(F)(F)F)=O.[CH3:8][O:9][C:10]1[CH:30]=[CH:29][C:13]([CH2:14][N:15]2[C:19]3[N:20]=[CH:21][C:22]4[CH2:23][CH:24]([NH2:28])[CH2:25][CH2:26][C:27]=4[C:18]=3[CH:17]=[N:16]2)=[CH:12][CH:11]=1.CCN(CC)CC.[C:38]1([S:44](Cl)(=[O:46])=[O:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[OH-].[Na+]>C1COCC1.CCOC(C)=O>[CH:17]1[C:18]2[C:27]3[CH2:26][CH2:25][CH:24]([NH:28][S:44]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)(=[O:46])=[O:45])[CH2:23][C:22]=3[CH:21]=[N:20][C:19]=2[NH:15][N:16]=1.[CH3:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([CH2:14][N:15]2[C:19]3[N:20]=[CH:21][C:22]4[CH2:23][CH:24]([NH:28][S:44]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)(=[O:46])=[O:45])[CH2:25][CH2:26][C:27]=4[C:18]=3[CH:17]=[N:16]2)=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 7369Benzenesulfonyl chlorideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 67426214HCID 67426214, compound

Product 2

HCID 46836620HCID 46836620, compoundHCID 67425880HCID 67425880, compoundYield 124.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(4-methoxy-benzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-ylamine TFA salt (0.156 g, 0.37 mmol) in anhydrous THF (5 mL) and Et3N (0.15 mL, 1.11 mmol) was added benzenesulfonyl chloride (60 μL, 0.46 mmol). The reaction mixture was shaken at room temperature for 3 hours followed by addition of EtOAc (20 mL) and 1.0M NaOH (15 mL). The organic layer was then separated, washed with brine (2×10 mL) and concentrated under reduced pressure to give the crude product. The crude product was purified using flash column chromatography (SiO2, 33% EtOAc in hexane) to give the desired product, N-(3-(4-methoxybenzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-7-yl)benzenesulfonamide as a white solid (0.103 g, 62%). Alternatively the crude product could be used in the next step without any further purification. M.p.>70° C.; 1H NMR (400 MHz, DMSO-d6) δ7.99 (s, 1H), 7.91 (s, 1H), 7.86 (m, 2H), 7.81 (s, 1H), 7.68-7.58 (m, 3H), 7.14 (m, 2H), 6.83 (m, 2H), 5.50 (s, 2H), 3.68 (s, 3H), 3.48 (m, 1H), 2.96 (m, 3H), 2.76 9m, 1H), 1.91 (m, 1H), 1.77 (m, 1H); LCMS [M+H]: 449.

Workup

  1. customThe organic layer was then separated
  2. washwashed with brine (2×10 mL)
  3. concentrationconcentrated under reduced pressure
  4. customto give the crude product
  5. customThe crude product was purified

Sources & evidence

ORD record
ord-42153b745bfa49db893a87c3f60dfe3e
Source dataset
uspto-grants-2012_09
Patent number
US08263610B2

Reaction notes

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