Triethylamine → HCID 89815336, compound

HRID 2172332Notes

Reaction equation

HRID 2172332 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:14]=1[CH2:15][CH2:16][NH:17][CH2:18]2.C(N(CC)CC)C.[S:30](Cl)([Cl:33])(=[O:32])=[O:31]>C(Cl)Cl>[Br:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:14]=1[CH2:15][CH2:16][N:17]([S:30]([Cl:33])(=[O:32])=[O:31])[CH2:18]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 24648Sulfuryl chlorideHCID 89813562HCID 89813562, compound2×

Product 1

HCID 89815336HCID 89815336, compoundYield 76.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 15-mL round-bottom flask was charged with 5-(2-bromo-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (Intermediate D, 287.2 mg, 0.731 mmol) and triethylamine (224 μl, 1.609 mmol) in DCM (3.8 mL) to give a brown solution. The flask was cooled in an ice-bath for 10 min, then sulfuryl chloride (125 μl, 1.536 mmol) was added dropwise. Stirring was continued for 2 hours at which time the mixture was quenched with water, then extracted with DCM (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was chromatographed on a 40 g silica gel column with 0 to 40% EtOAc/Heptane to give 5-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-sulfonyl chloride (253.01 mg, 0.556 mmol) as a clear, very viscous oil that was immediately used in the next step. A vial was charged with 5-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-sulfonyl chloride (40.045 mg, 0.088 mmol), pyrimidin-4-amine (41.9 mg, 0.440 mmol), chloroform (587 μl), and pyridine (71.2 μl, 0.881 mmol) and was placed into a 50° C. bath. The mixture was heated overnight before being allowed to cool to rt. The mixture was concentrated under a vacuum, and the residue was chromatographed on a 12 g silica gel column with 0 to 6% MeOH/DCM to give 5-(2-bromo-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (29.77 mg, 0.058 mmol) as a yellow solid. [M+H]+=513.0. 1H NMR (400 MHz, DMSO-d6) δ ppm=9.55 (br. s., 1H), 9.07 (br. s., 1H), 8.57 (br. s., 1H), 8.13 (d, J=1.3 Hz, 1H), 7.99 (br. s., 1H), 7.83 (dd, J=1.1, 8.0 Hz, 1H), 7.55-7.44 (m, 1H), 7.35-7.21 (m, 2H), 7.02 (dd, J=2.0, 6.8 Hz, 1H), 4.71 (d, J=6.4 Hz, 1H), 4.32-4.17 (m, 2H), 3.24-3.07 (m, 2H), 2.45 (br. s., 2H).

Workup

  1. customto give a brown solution
  2. temperatureThe flask was cooled in an ice-bath for 10 min
  3. customthe mixture was quenched with water
  4. extractionextracted with DCM (3×)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed on a 40 g silica gel column with 0 to 40% EtOAc/Heptane

Sources & evidence

ORD record
ord-0de5537ebf574513b326c875fbbaa7bc
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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