4-Iodoaniline → HCID 59426272, compound

HRID 502286Notes

Reaction equation

HRID 502286 reaction equation
[CH:1]1([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([N:14]4[CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)[CH:12]=3)[C:7]([C:20]#[N:21])=[CH:6]2)[CH2:4][CH2:3][CH2:2]1.C(OB(OC(C)C)OC(C)C)(C)C.[Li+].CC([N-]C(C)C)C.I[C:44]1[CH:50]=[CH:49][C:47]([NH2:48])=[CH:46][CH:45]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.Cl[Pd]Cl.CN(C=O)C>[NH2:48][C:47]1[CH:49]=[CH:50][C:44]([C:6]2[N:5]([CH:1]3[CH2:2][CH2:3][CH2:4]3)[C:13]3[C:8]([C:7]=2[C:20]#[N:21])=[CH:9][CH:10]=[C:11]([N:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)[CH:12]=3)=[CH:45][CH:46]=1

Participants

9

Reactant 5

HCID 108934-IodoanilineHCID 11430Potassium CarbonateHCID 21531Triisopropyl borateHCID 2724682Lithium diisopropylamideHCID 59426169HCID 59426169, compound

Product 1

HCID 59426272HCID 59426272, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-cyclobutyl-6-morpholin-4-yl-1H-indole-3-carbonitrile (1.20 g, 4.27 mmol), triisopropylborate (1.28 mL, 5.55 mmol) in THF (15 mL) at −78° C. was added LDA (1.5M mono THF in cyclohexane, 3.27 mL, 4.91 mmol) with stirring. The mixture was stirred at −78° C. for 10 minutes and at room temperature for 30 min followed by the addition of 4-iodoaniline (1.03 g, 4.70 mmol) and PdCl2 (dppf) (0.16 g, 0.2 mmol). The reaction system was cooled to −78° C., flushed with nitrogen followed by the addition of DMF (30 mL) and aq. K2CO3 (2.0M, 6.4 mL, 12.8 mmol). The cooling bath was removed and the mixture was stirred overnight and poured into ice water (500 mL). The precipitate was filtered, washed with water, dried in air and purified on silica gel (CH2Cl2/EtOAc, 9:1) to give 2-(4-amino-phenyl)-1-cyclobutyl-6-morpholin-4-yl-1H-indole-3-carbonitrile (1.49 g, 94%).

Workup

  1. stirringThe mixture was stirred at −78° C. for 10 minutes and at room temperature for 30 min
  2. customflushed with nitrogen
  3. customThe cooling bath was removed
  4. stirringthe mixture was stirred overnight
  5. additionpoured into ice water (500 mL)
  6. filtrationThe precipitate was filtered
  7. washwashed with water
  8. customdried in air
  9. custompurified on silica gel (CH2Cl2/EtOAc, 9:1)

Sources & evidence

ORD record
ord-edff76e007f84a5f8accadbb90fa8214
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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