Methylamine → HCID 86687497, compound

HRID 1473451Notes

Reaction equation

HRID 1473451 reaction equation
Cl[C:2]1[N:3]=[C:4]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:22]=2[O:31][CH3:32])[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([S:12]([NH:15][C:16]1[S:17][CH:18]=[CH:19][N:20]=1)(=[O:14])=[O:13])=[CH:7][CH:6]=2.[CH3:33][NH2:34].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CO.CC(C1C=C(C(C)C)C(C2C(OC)=CC(Cl)=C(OC)C=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.[Pd+2]>[CH3:32][O:31][C:22]1[CH:23]=[C:24]([C:27]([F:30])([F:29])[F:28])[CH:25]=[CH:26][C:21]=1[C:4]1[C:5]2[C:10](=[CH:9][C:8]([S:12]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:7][CH:6]=2)[CH:11]=[C:2]([NH:34][CH3:33])[N:3]=1

Participants

6

Reactant 3

HCID 6329MethylamineHCID 2733832Lithium HexamethyldisilazideHCID 86687494HCID 86687494, compound

Product 1

HCID 86687497HCID 86687497, compoundYield 85.3%

Reagents, catalysts & solvents 2

HCID 75412134Dicyclohexyl(2 inverted exclamation mark,4 inverted exclamation mark,6 inverted exclamation mark-Triisopropyl-3,6-Dimethoxy-[1,1 inverted exclamation mark-Biphenyl]-2-Yl)Phosphine-(2-(2-Aminoethyl)Phenyl)Palladium(Ii) ChlorideCatalystHCID 887MethanolSolvent

Procedure

A vial was charged with 3-chloro-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Example 249) (34.13 mg, 0.068 mmol) and chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(ii) (Strem Chemical, Newburyport, Mass.) (5.45 mg, 6.83 μmol), then flushed with Ar (g). Methanamine (2M in THF) (341 μl, 0.683 mmol) was added to give a solution. Lithium bis(trimethylsilyl)amide (1M in THF) (341 μl, 0.341 mmol) was added, resulting in the formation of a maroon solution. After 15 min, the mixture was diluted with MeOH and concentrated. The residue was purified by chromatography on silica gel (12-g column, 0 to 10% MeOH/DCM) to give 1-(2-methoxy-4-(trifluoromethyl)phenyl)-3-(methylamino)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (28.58 mg, 0.058 mmol, 85% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.81 (br. s., 1H), 8.11 (d, J=1.6 Hz, 1H), 7.53-7.42 (m, 3H), 7.36-7.24 (m, 3H), 6.88-6.82 (m, 1H), 6.79-6.71 (m, 2H), 3.75 (s, 3H), 2.82 (d, J=5.0 Hz, 3H); m/z (ESI) 495.2 (M+H)+.

Workup

  1. customflushed with Ar (g)
  2. customto give a solution
  3. customresulting in the formation of a maroon solution
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography on silica gel (12-g column, 0 to 10% MeOH/DCM)

Sources & evidence

ORD record
ord-e40f359248714deb9b913093b5cccfb2
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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