1,4-Dioxane → HCID 86687376, compound

HRID 1473324Notes

Reaction equation

HRID 1473324 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[C:21]2[C:16](=[CH:17][C:18]([S:22]([NH:25][C:26]3[CH:31]=[CH:30][N:29]=[CH:28][N:27]=3)(=[O:24])=[O:23])=[CH:19][CH:20]=2)[CH:15]=[CH:14][N:13]=1.[CH3:32][N:33]1[CH2:38][CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH2:35][CH2:34]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[CH3:32][N:33]1[CH2:34][CH:35]=[C:36]([C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=2[C:12]2[C:21]3[C:16](=[CH:17][C:18]([S:22]([NH:25][C:26]4[CH:31]=[CH:30][N:29]=[CH:28][N:27]=4)(=[O:24])=[O:23])=[CH:19][CH:20]=3)[CH:15]=[CH:14][N:13]=2)[CH2:37][CH2:38]1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 207733711-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 86687377HCID 86687377, compound

Product 1

HCID 86687376HCID 86687376, compoundYield 95.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 1-(2-bromo-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (42.16 mg, 0.083 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (27.7 mg, 0.124 mmol) Pd(AmPhos)2Cl2 (2.93 mg, 4.14 μmol), potassium phosphate (52.7 mg, 0.248 mmol), dioxane (414 μl), and water (138 μl). The vial was sealed and heated in a microwave reactor for 30 min at 100° C. The mixture was extracted with EtOAc (three times). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel, eluting with 5 to 10% MeOH/DCM, then with 15% MeOH/EtOAc, and finally with a solution of 20% of 2N ammonia in methanol in DCM. The fractions containing product were collected and concentrated. The residue was dissolved in DCM and filtered through cotton. The filtrate was concentrated to give 1-(2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (41.4 mg, 0.079 mmol) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.63 (d, J=5.7 Hz, 1H), 8.55 (d, J=1.5 Hz, 1H), 8.35 (s, 1H), 8.08 (d, J=5.8 Hz, 1H), 8.01 (d, J=6.2 Hz, 1H), 7.91 (dd, J=1.8, 8.9 Hz, 1H), 7.83 (d, J=8.1 Hz, 1H), 7.76 (s, 1H), 7.63 (dd, J=8.4, 19.4 Hz, 2H), 6.72 (d, J=6.2 Hz, 1H), 5.37 (br. s., 1H), 2.98 (br. s., 2H), 2.52 (br. s., 2H), 2.20 (s, 3H), 2.16-1.96 (m, 2H). m/z (ESI) 526.2 (M+H)+.

Workup

  1. customThe vial was sealed
  2. extractionThe mixture was extracted with EtOAc (three times)
  3. concentrationThe combined organic extracts were concentrated
  4. customThe residue was purified by chromatography on silica gel
  5. washeluting with 5 to 10% MeOH/DCM
  6. additionThe fractions containing product
  7. customwere collected
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in DCM
  10. filtrationfiltered through cotton
  11. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-fbeb5c9b89f04ca5b3b67c67c1fe5333
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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