Potassium Phosphate, Tribasic → HCID 71736587, compound

HRID 2172309Notes

Reaction equation

HRID 2172309 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.CC1(C)C(C)(C)OB([C:26]2[CH:35]=[CH:34][CH:33]=[C:32]3[C:27]=2[CH2:28][CH2:29][N:30]([S:36]([NH:39][C:40]2[S:44][N:43]=[CH:42][N:41]=2)(=[O:38])=[O:37])[CH2:31]3)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O>[O:15]1[CH2:16][CH2:17][N:12]([C:3]2[CH:4]=[C:5]([C:8]([F:11])([F:10])[F:9])[CH:6]=[CH:7][C:2]=2[C:26]2[CH:35]=[CH:34][CH:33]=[C:32]3[C:27]=2[CH2:28][CH2:29][N:30]([S:36]([NH:39][C:40]2[S:44][N:43]=[CH:42][N:41]=2)(=[O:37])=[O:38])[CH2:31]3)[CH2:13][CH2:14]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 89813599HCID 89813599, compound2×HCID 89815245HCID 89815245, compound2×

Product 1

HCID 71736587HCID 71736587, compoundYield 9.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 0.023 g, 0.033 mmol), 4-(2-bromo-5-(trifluoromethyl)phenyl)morpholine (Intermediate G, 0.154 g, 0.497 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (Intermediate F, 0.140 g, 0.331 mmol), and potassium phosphate (0.281 g, 1.326 mmol) in 2.5 mL dioxane and 1 mL water was heated to 100° C. 2 hours. The reaction mixture was cooled to rt, diluted with EtOAc and washed with 1 N citric acid solution. The organic layers were dried over MgSO4 and concentrated. Purification of the resulting residue by reverse phase column chromatography [RediSep Gold C-18 50 g, 5 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 5-(2-morpholino-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.016 g, 0.030 mmol). [M+H]+=525.8 1H NMR (400 MHz, Acetone-d6) δ ppm: 8.23 (s, 1H), 7.38-7.44 (m, 1H), 7.26-7.36 (m, 3H), 7.14-7.22 (m, 2H), 4.35-4.40 (m, 2H), 3.39-3.49 (m, 3H), 3.28-3.38 (m, 2H), 2.86-2.96 (m, 2H), 2.73-2.81 (m, 2H), 2.47-2.60 (m, 1H)

Workup

  1. custom2 hours
  2. washwashed with 1 N citric acid solution
  3. dry with materialThe organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. customPurification of the resulting residue by reverse phase column chromatography [RediSep Gold C-18 50 g, 5 to 100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-9d5ad990591a4d6abe6b0d6ad5621a22
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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