Diisopropylamine → 2-(2-Chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-6-sulfonic acid benzhydrylamide

HRID 1986206Notes

Reaction equation

HRID 1986206 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH:13]([NH:26][S:27]([C:30]1[CH:31]=[CH:32][C:33]2[CH:37]=[CH:36][S:35][C:34]=2[CH:38]=1)(=[O:29])=[O:28])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(OB(OC(C)C)OC(C)C)(C)C.C(=O)([O-])[O-].[Na+].[Na+].[Cl:58][C:59]1[N:64]=[C:63](Cl)[C:62]([CH3:66])=[CH:61][N:60]=1>C1COCC1.O>[CH:13]([NH:26][S:27]([C:30]1[CH:31]=[CH:32][C:33]2[CH:37]=[C:36]([C:61]3[C:62]([CH3:66])=[CH:63][N:64]=[C:59]([Cl:58])[N:60]=3)[S:35][C:34]=2[CH:38]=1)(=[O:29])=[O:28])([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

9

Reactant 6

HCID 7912DiisopropylamineHCID 10340Sodium CarbonateHCID 21531Triisopropyl borateHCID 74508Pyrimidine, 2,4-dichloro-5-methyl-HCID 68857528Benzo[b]thiophene-6-sulfonic acid benzhydrylamideHCID 178418339Butyllithium

Product 1

HCID 866253552-(2-Chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-6-sulfonic acid benzhydrylamideYield 37%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
10 °C

Procedure

To a solution of diisopropylamine (2.09 mL, 14.87 mmol) in dry THF (10 mL) is added a solution of n-butyllithium (1.6 M in hexane, 9.14 mL, 14.62 mmol) at −78° C. under a nitrogen atmosphere, the mixture is stirred for 30 minutes. A solution of benzo[b]thiophene-6-sulfonic acid benzhydrylamide (925 mg, 2.44 mmol) and triisopropylborate (2.87 mL, 12.43 mmol) in dry THF (10 mL) is added. The mixture is slowly warmed to 10° C. over 1 hour and stirred at room temperature for 30 minutes. A solution of sodium carbonate (2 M in water, 3.78 mL) is added followed by the addition of 2,4 dichloro5-methylpyrimidine (517 mg, 3.17 mmol) and (1,1′-bis(diphenylphosphino)ferrocene)palladium (II) chloride (99.6 mg, 0.122 mmol). The mixture is heated at 60° C. for 1.5 hours then cooled to room temperature. Water (40 mL) is added and the mixture is extracted with EtOAc (3×40 mL). The organic layers are dried (MgSO4) and concentrated. The residue is chromatographed on silica gel, eluting with hexanes/EtOAc 90:10 to 40:60, to give the title compound as a yellow solid (457 mg, 37% yield).

Workup

  1. stirringstirred at room temperature for 30 minutes
  2. temperatureThe mixture is heated at 60° C. for 1.5 hours
  3. temperaturethen cooled to room temperature
  4. extractionthe mixture is extracted with EtOAc (3×40 mL)
  5. dry with materialThe organic layers are dried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel
  8. washeluting with hexanes/EtOAc 90:10 to 40:60

Sources & evidence

ORD record
ord-c1bff4ebd6b84dd98f8eb20b27916ce9
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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