Methanesulfonyl chloride → 4-((2-(Ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-(methylsulfonamidomethyl)isoquinolin-3-yl methanesulfonate

HRID 1620246Notes

Reaction equation

HRID 1620246 reaction equation
C([O:4][C:5]1[N:6]=[C:7]([CH2:35][NH:36]C(=O)C)[C:8]2[C:13]([C:14]=1[CH2:15][C:16]1[C:17]([NH:28][CH2:29][CH3:30])=[N:18][C:19]3[C:24]([CH:25]=1)=[CH:23][C:22]([O:26][CH3:27])=[CH:21][CH:20]=3)=[CH:12][C:11]([O:31][CH3:32])=[C:10]([O:33][CH3:34])[CH:9]=2)(=O)C.CC(N(C(C)C)CC1C=CC=CC=1)C.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1.[CH3:72][S:73](Cl)(=[O:75])=[O:74]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:72][S:73]([O:4][C:5]1[N:6]=[C:7]([CH2:35][NH:36][S:73]([CH3:72])(=[O:75])=[O:74])[C:8]2[C:13]([C:14]=1[CH2:15][C:16]1[C:17]([NH:28][CH2:29][CH3:30])=[N:18][C:19]3[C:24]([CH:25]=1)=[CH:23][C:22]([O:26][CH3:27])=[CH:21][CH:20]=3)=[CH:12][C:11]([O:31][CH3:32])=[C:10]([O:33][CH3:34])[CH:9]=2)(=[O:75])=[O:74]

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 16212447N-benzyl-N-propan-2-ylpropan-2-amine;1,4-bis(ethenyl)benzene;styreneHCID 601638771-(Acetamidomethyl)-4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-yl acetate

Product 1

HCID 866698234-((2-(Ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-(methylsulfonamidomethyl)isoquinolin-3-yl methanesulfonate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

The other portion of the residue CCH 42006-2 (see preparation of compound 56) was transferred in a 5 mL microwave vial equipped with a magnetic stirrer before addition of diisopropylaminomethyl-polystyrene resin (3 mmol/g, 86 mg, 258 μmol), DMAP (2 mg, 16 μmol) and methanesulfonyl chloride (25 μL, 323 μmol) and the reaction mixture was stirred for 20 min at 100° C. under microwave irradiation. After cooling to RT, the mixture was diluted with CH2Cl2 (30 mL), filtered through cotton wool, then washed with brine (5 mL), dried over Na2SO4, filtered, and concentrated under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 0:100) gave 4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-(methylsulfonamidomethyl)isoquinolin-3-yl methanesulfonate as a pale yellow solid.

Workup

  1. temperatureAfter cooling to RT
  2. filtrationfiltered through cotton wool
  3. washwashed with brine (5 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customPurification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 0:100)

Sources & evidence

ORD record
ord-dd6444e138784ff7839154d24e1a8d5e
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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