Triethylamine → HCID 86613378, compound

HRID 2422882Notes

Reaction equation

HRID 2422882 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([C@H:14]([NH2:16])[CH3:15])=[CH:10][CH:9]=2)=[CH:6][C:5]([F:17])=[CH:4][N:3]=1.C(N(CC)CC)C.[F:25][C:26]1[CH:27]=[C:28]([S:33](Cl)(=[O:35])=[O:34])[CH:29]=[CH:30][C:31]=1[F:32]>ClCCl>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[CH:10][C:11]([C@H:14]([NH:16][S:33]([C:28]3[CH:29]=[CH:30][C:31]([F:32])=[C:26]([F:25])[CH:27]=3)(=[O:35])=[O:34])[CH3:15])=[CH:12][CH:13]=2)=[CH:6][C:5]([F:17])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27369133,4-Difluorobenzene-1-sulfonyl chlorideHCID 86613379HCID 86613379, compound

Product 1

HCID 86613378HCID 86613378, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2-[1-(4-bromo-phenyl)-ethyl]-isoindole-1,3-dione (1.19 g, 3.6 mmol) (Example 26) in 1,2-dimethoxyethane (3 ml) was added 2-chloro-5-fluoropyridine-3-boronic acid (0.95 g, 5.4 mmol), tetrakis(triphenylphosphine)palladium (0) (0.21 g, 0.2 mmol) and 2M aqueous sodium carbonate (3.2 ml, 6.4 mmol). The reaction mixture was heated in a microwave oven at 150° C. for 10 min and the solvent evaporated. The residue was partitioned between ethyl acetate and water. The organic phase washed with brine, dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified over silica gel eluting with heptane/ethyl acetate to give (R)-2-{1-[4-(2-chloro-5-fluoro-pyridin-3-yl)-phenyl]-ethyl}-isoindole-1,3-dione (0.62 g, 1.6 mmol, 44%) as a clear glass. To a solution of (R)-2-[1-(4-bromo-phenyl)-ethyl]-isoindole-1,3-dione (0.16 g, 0:4 mmol) in methanol (4 ml) was added hydrazine hydrate (0.43 g, 8.6 mmol). The reaction mixture was stirred at room temperature for 18 h and then concentrated under reduced pressure. Dichloromethane was added and the resultant white precipitate filtered off. The solvent was evaporated to give 1-[4-(2-chloro-5-fluoro-pyridin-3-yl)-phenyl]-ethylamine (0.11 g, 0.4 mmol, 100%) as a yellow gum. To a solution of (R)-1-[4-(2-chloro-5-fluoro-pyridin-3-yl)-phenyl]-ethylamine (26 mg, 0.1 mmol) in dichloromethane (1 ml) was added triethylamine (31.6 mg, 0.31 mmol) followed by 3,4-difluorobenzenesulfonyl chloride (28.7 mg, 0.14 mmol). The reaction mixture was agitated for 64 h at room temperature and the solvent evaporated. The crude product was taken up in dimethyl sulfoxide (1 ml) and purified by preparatory LCMS. The solvent was evaporated under reduced pressure to give the title compound (6.7 mg, 0.04 mmol, 38%). 1H NMR (400 MHz, DMSO-d6): δ 8.48 (m, 2H), 7.78 (dd, 1H), 7.45-7.60 (m, 3H), 7.27-7.34 (m, 4H), 4.50 (q, 1H), 1.33 (d, 3H) ppm; MS (ESI) m/z: 427 [M+H]+.

Workup

  1. customthe solvent evaporated
  2. custompurified by preparatory LCMS
  3. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-e417b4b125d041b8b4d5523c715003b6
Source dataset
uspto-grants-2011_06
Patent number
US07960365B2

Reaction notes

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