8-Hydroxyquinoline → HCID 11489278, compound

HRID 1593081Notes

Reaction equation

HRID 1593081 reaction equation
C(OC(=O)[N:7]([C:9]1[C:10]([CH3:29])=[C:11]2[C:16](=[CH:17][C:18]=1[F:19])[C:15](=[O:20])[N:14]([CH2:21]OCC[Si](C)(C)C)[CH:13]=[CH:12]2)[CH3:8])(C)(C)C.C(O)(C(F)(F)F)=O.IC1[CH:45]=[CH:44][C:42]([NH2:43])=[CH:41][CH:40]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[K+].[K+].C([O:65][C:66](=O)[NH:67][S:68]([C:71]1[S:72][C:73]([Cl:76])=[CH:74][CH:75]=1)(=[O:70])=[O:69])C>CS(C)=O.C(OCC)(=O)C.[Cu]I>[Cl:76][C:73]1[S:72][C:71]([S:68]([NH:67][C:66]([NH:43][C:42]2[CH:41]=[CH:40][C:21]([N:14]3[CH:13]=[CH:12][C:11]4[C:16](=[CH:17][C:18]([F:19])=[C:9]([NH:7][CH3:8])[C:10]=4[CH3:29])[C:15]3=[O:20])=[CH:45][CH:44]=2)=[O:65])(=[O:70])=[O:69])=[CH:75][CH:74]=1

Participants

10

Reactant 6

HCID 19238-HydroxyquinolineHCID 6422Trifluoroacetic acidHCID 108934-IodoanilineHCID 11430Potassium CarbonateHCID 24778122Ethyl ((5-chlorothiophen-2-yl)sulfonyl)carbamateHCID 58998413HCID 58998413, compound

Product 1

HCID 11489278HCID 11489278, compoundYield 19.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

[7-Fluoro-5-methyl-1-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-isoquinolin-6-yl]-methyl-carbamic acid tert-butyl ester (44 mg, 0.10 mmol, Example 119) was treated with TFA for 1 h and concentrated in vacuo. Treatment of this crude material with 25 mg (0.115 mmol) of p-iodoaniline, 4 mg of CuI, 3 mg 8-hydroxyquinoline and 17 mg of K2CO3 in 200 μL of DMSO at 120° C. for 18 hrs, after which the reaction was cooled to room temperature, diluted with ethyl acetate and washed with brine. The combined organic layers were dried over Na2SO4 and concentrated in vacuo to give a crude residue, which was subjected to coupling with 57 mg of (5-Chloro-thiophene-2-sulfonyl)-carbamic acid ethyl ester as described in Example 13, gave 10 mg of 5-chloro-N-[({4-[7-fluoro-5-methyl-6-(methylamino)-1-oxoisoquinolin-2(1H)-yl]phenyl}amino)carbonyl]thiophene-2-sulfonamide after RP-HPLC purification. ES-MS (M+H)+=521.1 (Cl).

Workup

  1. concentrationconcentrated in vacuo
  2. washwashed with brine
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customto give a crude residue, which

Sources & evidence

ORD record
ord-5d39e539b46342d786265d6159d82ff3
Source dataset
uspto-grants-2007_11
Patent number
US07294635B2

Reaction notes

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