Potassium Carbonate → [4-(6-bromo-3-cyano-1-cyclobutyl-1H-indol-2-yl)-phenyl]-carbamic acid tert-butyl ester

HRID 1009669Notes

Reaction equation

HRID 1009669 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:15]#[N:16])=[CH:7][N:8]2[CH:11]2[CH2:14][CH2:13][CH2:12]2)=[CH:4][CH:3]=1.C(OB(OC(C)C)OC(C)C)(C)C.[Li+].CC([N-]C(C)C)C.[C:38]([O:42][C:43](=[O:52])[NH:44][C:45]1[CH:50]=[CH:49][C:48](I)=[CH:47][CH:46]=1)([CH3:41])([CH3:40])[CH3:39].C([O-])([O-])=O.[K+].[K+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[C:38]([O:42][C:43](=[O:52])[NH:44][C:45]1[CH:46]=[CH:47][C:48]([C:7]2[N:8]([CH:11]3[CH2:14][CH2:13][CH2:12]3)[C:9]3[C:5]([C:6]=2[C:15]#[N:16])=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=3)=[CH:49][CH:50]=1)([CH3:41])([CH3:39])[CH3:40]

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 21531Triisopropyl borateHCID 2724682Lithium diisopropylamideHCID 2773612tert-butyl N-(4-iodophenyl)carbamateHCID 594304766-bromo-1-cyclobutyl-1H-indole-3-carbonitrile

Product 1

HCID 59430631[4-(6-bromo-3-cyano-1-cyclobutyl-1H-indol-2-yl)-phenyl]-carbamic acid tert-butyl esterYield 53%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 6-bromo-1-cyclobutyl-1H-indole-3-carbonitrile (1.38 g, 5.0 mmol), and triisopropylborate (1.37 mL, 6.0 mmol) in THF (15.0 mL) at −78° C. was added LDA (1.5M mono THF in cyclohexane, 3.83 mL, 5.75 mmol) with stirring. The mixture was stirred at −78° C. for 10 min and at room temperature for 30 min followed by addition of (4-iodophenyl)-carbamic acid tert-butyl ester (1.75 g, 5.5 mmol) and PdCl2(dppf) (0.37 g, 0.5 mmol). The reaction mixture was cooled to −78° C., flushed with nitrogen and DMF (30 mL) and aq. K2CO3 (2.0M, 7.5 mL, 15.0 mmol) added. The mixture was stirred at −78° C. for 20 min, room temperature overnight and poured into ice water (200 mL). The precipitate was filtered, washed with water and purified on silica gel (hexanes/EtOAc, 9:1 to 8:2) to give [4-(6-bromo-3-cyano-1-cyclobutyl-1H-indol-2-yl)-phenyl]-carbamic acid tert-butyl ester as a solid (1.23 g, 53%).

Workup

  1. stirringThe mixture was stirred at −78° C. for 10 min and at room temperature for 30 min
  2. additionadded
  3. stirringThe mixture was stirred at −78° C. for 20 min, room temperature overnight
  4. filtrationThe precipitate was filtered
  5. washwashed with water
  6. custompurified on silica gel (hexanes/EtOAc, 9:1 to 8:2)

Sources & evidence

ORD record
ord-b1907ba25cd540d6aacddbd8c68ef73b
Source dataset
uspto-grants-2011_07
Patent number
US07973069B2

Reaction notes

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