Potassium Carbonate → (R)-tert-Butyl (1-(3-(methylthio)-1-(5-phenylpyrimidin-2-yl)-1H-indole-6-carbonyl)pyrrolidin-3-yl)carbamate

HRID 630501Notes

Reaction equation

HRID 630501 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[C:8]1[CH:9]=[N:10][C:11]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:23]([N:25]4[CH2:29][CH2:28][C@@H:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26]4)=[O:24])[CH:21]=3)[C:16]([S:38][CH3:39])=[CH:15]2)=[N:12][CH:13]=1.[C:40]1(B(O)O)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(O)(C)(C)C.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:39][S:38][C:16]1[C:17]2[C:22](=[CH:21][C:20]([C:23]([N:25]3[CH2:29][CH2:28][C@@H:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26]3)=[O:24])=[CH:19][CH:18]=2)[N:14]([C:11]2[N:10]=[CH:9][C:8]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[CH:13][N:12]=2)[CH:15]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 131735396(R)-tert-Butyl (1-(1-(5-bromopyrimidin-2-yl)-3-(methylthio)-1H-indole-6-carbonyl)pyrrolidin-3-yl)carbamate

Product 1

HCID 131735397(R)-tert-Butyl (1-(3-(methylthio)-1-(5-phenylpyrimidin-2-yl)-1H-indole-6-carbonyl)pyrrolidin-3-yl)carbamate

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 714019492-Methylpropan-2-ol--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

Potassium carbonate (1.16 g, 8.45 mmol) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.2 g, 0.28 mmol) were added under an argon atmosphere and at room temperature to a solution of 223b) (1.5 g, 2.8 mmol) and phenyl boronic acid (0.69 g, 5.63 mmol) in tert-butanol/water (10:1, 66 mL). The resulting mixture was heated at 90° C. for 2 h, then cooled to room temperature and filtered through a pad of celite. The filtrate was concentrated and the remnant purified by flash column chromatography [silica gel, dichloromethane with 2% methanol] and then triturated with ether. White solid. Yield: 1 g (67% of theory)

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through a pad of celite
  3. concentrationThe filtrate was concentrated
  4. customthe remnant purified by flash column chromatography [silica gel, dichloromethane with 2% methanol]
  5. customtriturated with ether

Sources & evidence

ORD record
ord-d24434a30faf4493af16883ebe32cddf
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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