Potassium Carbonate → 1-cyclopropyl-6-hydroxy-2-(4-isopropylamino-phenyl)-1H-indole-3-carbonitrile

HRID 1009667Notes

Reaction equation

HRID 1009667 reaction equation
[CH:1]1([N:4]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([OH:13])[CH:11]=3)[C:6]([C:14]#[N:15])=[CH:5]2)[CH2:3][CH2:2]1.C(OB(O[CH:26]([CH3:28])[CH3:27])OC(C)C)(C)C.[Li+].CC([N-]C(C)C)C.C1([C@H](OC(=O)[NH:44][C:45]2[CH:50]=[CH:49][C:48](I)=[CH:47][CH:46]=2)C)CC1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.Cl[Pd]Cl.CN(C=O)C>[CH:1]1([N:4]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([OH:13])[CH:11]=3)[C:6]([C:14]#[N:15])=[C:5]2[C:48]2[CH:49]=[CH:50][C:45]([NH:44][CH:26]([CH3:27])[CH3:28])=[CH:46][CH:47]=2)[CH2:3][CH2:2]1

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 21531Triisopropyl borateHCID 2724682Lithium diisopropylamideHCID 59430460(R)-(4-iodo-phenyl)carbamic acid 1-cyclopropyl-ethyl esterHCID 594306891-cyclopropyl-6-hydroxy-1H-indole-3-carbonitrile

Product 1

HCID 594306811-cyclopropyl-6-hydroxy-2-(4-isopropylamino-phenyl)-1H-indole-3-carbonitrile

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-cyclopropyl-6-hydroxy-1H-indole-3-carbonitrile (0.59 g, 3.0 mmol), triisopropylborate (1.03 mL, 4.5 mmol) in THF (15 mL) at −78° C. was added LDA (1.5M mono THF in cyclohexane, 4.60 mL, 6.9 mmol) with stirring. The mixture was stirred at −78° C. for 10 min and at room temperature for 30 min, followed by the addition of (R)-(4-iodo-phenyl)-carbamic acid 1-cyclopropyl-ethyl ester (1.19 g, 3.6 mmol) and PdCl2 (dppf) (0.11 g, 0.15 mmol). The reaction mixture was cooled to −78° C., flushed with nitrogen and DMF (30 mL) and aq. K2CO3 (2.0M, 4.5 mL, 9.0 mmol) added. The cooling bath was removed and the mixture was stirred overnight, poured into ice water (100 mL) and neutralized with acetic acid. The precipitate was filtered, washed with water and CH2Cl2 and dried in air to provide 1-cyclopropyl-6-hydroxy-2-(4-isopropylamino-phenyl)-1H-indole-3-carbonitrile as a solid (0.85 g, 86).

Workup

  1. stirringThe mixture was stirred at −78° C. for 10 min and at room temperature for 30 min
  2. additionadded
  3. customThe cooling bath was removed
  4. stirringthe mixture was stirred overnight
  5. additionpoured into ice water (100 mL)
  6. filtrationThe precipitate was filtered
  7. washwashed with water and CH2Cl2
  8. customdried in air

Sources & evidence

ORD record
ord-84ac8a00657e47d29d584a0bea80acf9
Source dataset
uspto-grants-2011_07
Patent number
US07973069B2

Reaction notes

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