Benzenesulfonyl chloride → HCID 131733393, compound

HRID 2274583Notes

Reaction equation

HRID 2274583 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][C:10]([C:14]([N:16]([CH2:21][CH2:22][CH2:23][CH3:24])[CH2:17][CH2:18][CH2:19][CH3:20])=[O:15])=[N:9]2)=[C:4]([C:25]([N:27]2[C@H:36]([CH2:37][O:38][Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])[CH2:35][C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:28]2)=[O:26])[CH:3]=1.CCN(CC)CC.[C:53]1([S:59](Cl)(=[O:61])=[O:60])[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>C(Cl)Cl.O>[CH2:17]([N:16]([CH2:21][CH2:22][CH2:23][CH3:24])[C:14]([C:10]1[CH:11]=[C:12]([CH3:13])[N:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][S:59]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)(=[O:61])=[O:60])=[CH:3][C:4]=2[C:25]([N:27]2[C@H:36]([CH2:37][O:38][Si:39]([C:42]([CH3:43])([CH3:45])[CH3:44])([CH3:41])[CH3:40])[CH2:35][C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:28]2)=[O:26])[N:9]=1)=[O:15])[CH2:18][CH2:19][CH3:20]

Participants

6

Reactant 3

HCID 7369Benzenesulfonyl chlorideHCID 8471TriethylamineHCID 89660279HCID 89660279, compound2×

Product 1

HCID 131733393HCID 131733393, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a ice-cooled solution of (S)-1-(4-amino-2-(3-(((tert-butyldimethylsilyl)oxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-5-methyl-1H-pyrazole-3-carboxamide (intermediate B, 0.20 g, 0.316 mmol) in DCM (2 mL) was added Et3N (0.05 mL, 0.47 mmol) and benzenesulfonyl chloride (0.06 g, 0.38 mmol) followed by stirring at RT for 16 h. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (100 mL). The organic layer was washed with brine (50 mL), dried over sodium sulphate and concentrated invacuo. The residue was purified on silica gel (100-200 mesh) to afford (S)—N,N-dibutyl-1-(2-(3-(((tert-butyldimethylsilyl)oxy)methyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(phenylsulfonamido)phenyl)-5-methyl-1H-pyrazole-3-carboxamide as a mixture of mono and bis sulfonamides, 0.21 g (crude). The crude reaction mass was used in the next reaction without further purification. Rf=0.75 (50% EtOAc in hexane); ES-MS: m/z 772.6 (M+H).

Workup

  1. extractionextracted with EtOAc (100 mL)
  2. washThe organic layer was washed with brine (50 mL)
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated invacuo
  5. customThe residue was purified on silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-291a000970404bbcb4a473b0365311c5
Source dataset
uspto-grants-2015_09
Patent number
US09126980B2

Reaction notes

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