Potassium Phosphate, Tribasic → methyl 3-(4-isopropylpyrimidin-2-yl)-1-tosyl-1H-indole-5-carboxylate

HRID 634205Notes

Reaction equation

HRID 634205 reaction equation
CC1(C)C(C)(C)OB([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([O:20][CH3:21])=[O:19])[CH:16]=3)[N:11]([S:22]([C:25]3[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=3)(=[O:24])=[O:23])[CH:10]=2)O1.Cl[C:34]1[N:39]=[C:38]([CH:40]([CH3:42])[CH3:41])[CH:37]=[CH:36][N:35]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:40]([C:38]1[CH:37]=[CH:36][N:35]=[C:34]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([O:20][CH3:21])=[O:19])[CH:16]=3)[N:11]([S:22]([C:25]3[CH:26]=[CH:27][C:28]([CH3:29])=[CH:30][CH:31]=3)(=[O:23])=[O:24])[CH:10]=2)[N:39]=1)([CH3:42])[CH3:41]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 249019162-Chloro-4-isopropylpyrimidineHCID 68328028methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole-5-carboxylate

Product 1

HCID 68327948methyl 3-(4-isopropylpyrimidin-2-yl)-1-tosyl-1H-indole-5-carboxylateYield 75.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A brown mixture of methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole-5-carboxylate (1.85 g, 4.06 mmol), 2-chloro-4-isopropylpyrimidine (0.700 g, 4.47 mmol) [CombiPhos Catalyst Inc.], potassium phosphate (2.59 g, 12.19 mmol), Pd2(dba)3 (0.15 g, 0.16 mmol), and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (X-Phos) (0.15 g, 0.32 mmol) in dioxane (15 mL) and H2O (3.00 mL) was purged with argon then heated in an oil bath at 100° C. for 3 h. The reaction was cooled to RT, diluted with EtOAc (100 mL), washed with NaOH (5 mL of 0.5 N) followed by brine (5 mL). The organic solution was dried and concentrated. Chromatographic purification of the brown residue (20-80% EtOAc/Hex) furnished methyl 3-(4-isopropylpyrimidin-2-yl)-1-tosyl-1H-indole-5-carboxylate (1.37 g, 75%) as a light-yellow solid. This material was used in next step without further purification. MS (ESI, pos. ion) m/z: 450.0 (M+1).

Workup

  1. customwas purged with argon
  2. temperatureThe reaction was cooled to RT
  3. additiondiluted with EtOAc (100 mL)
  4. washwashed with NaOH (5 mL of 0.5 N)
  5. customThe organic solution was dried
  6. concentrationconcentrated
  7. customChromatographic purification of the brown residue (20-80% EtOAc/Hex)

Sources & evidence

ORD record
ord-8534abe0469247d18d77a4e31587541a
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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