Potassium Phosphate, Tribasic → HCID 89815597, compound

HRID 2172303Notes

Reaction equation

HRID 2172303 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:8]=2B2OC(C)(C)C(C)(C)O2)=[CH:5][CH:4]=[N:3]1.Br[C:27]1[CH:36]=[CH:35][CH:34]=[C:33]2[C:28]=1[CH2:29][CH2:30][N:31]([S:37]([NH:40][C:41]1[S:42][CH:43]=[CH:44][N:45]=1)(=[O:39])=[O:38])[CH2:32]2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O>[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[C:11]([C:13]([F:14])([F:15])[F:16])[CH:10]=[CH:9][C:8]=2[C:27]2[CH:36]=[CH:35][CH:34]=[C:33]3[C:28]=2[CH2:29][CH2:30][N:31]([S:37]([NH:40][C:41]2[S:42][CH:43]=[CH:44][N:45]=2)(=[O:39])=[O:38])[CH2:32]3)=[CH:5][CH:4]=[N:3]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 898152081H-Pyrazole, 1-methyl-5-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)phenyl]-2×HCID 89815303HCID 89815303, compound

Product 1

HCID 89815597HCID 89815597, compoundYield 31.8%

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, 0.032 mmol), 1-methyl-5-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)phenyl)-1H-pyrazole (Intermediate O, 0.169 g, 0.481 mmol), 5-bromo-N-(thiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.120 g, 0.321 mmol), and potassium phosphate (0.272 g, 1.282 mmol) in 2.5 mL dioxane, 1.0 mL water was heated to 100° C. 4 hours. The reaction mixture was diluted with EtOAc and washed with 1 N citric acid solution. The organics were dried over MgSO4 and concentrated. Purification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (0.053 g, 0.102 mmol). [M+H]+=519.8 1H NMR (400 MHz, Acetone-d6) δ ppm: 7.88 (dd, J=8.0, 1.4 Hz, 1H), 7.81 (s, 1H), 7.63 (d, J=8.0 Hz, 1H), 7.25 (d, J=2.0 Hz, 1H), 7.09-7.17 (m, 3H), 6.98-7.01 (m, 1H), 6.71 (d, J=4.7 Hz, 1H), 6.00 (d, J=2.0 Hz, 1H), 4.31 (d, J=15.7 Hz, 1H), 4.24 (d, J=15.7 Hz, 1H), 3.30-3.38 (m, 1H), 3.12 (m, 1H), 2.63-2.74 (m, 1H), 2.36-2.46 (m, 1H)

Workup

  1. custom4 hours
  2. washwashed with 1 N citric acid solution
  3. dry with materialThe organics were dried over MgSO4
  4. concentrationconcentrated
  5. customPurification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane)

Sources & evidence

ORD record
ord-05e40fe330634d7c8bc3f266f9370a3f
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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