5-Indolylboronic acid → HCID 16755225, compound

HRID 408628Notes

Reaction equation

HRID 408628 reaction equation
[N:1]12[CH2:9][CH:5]([CH2:6][CH2:7][CH2:8]1)[CH:4]([NH:10][C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][N:12]=1)[CH2:3][CH2:2]2.[NH:18]1[C:26]2[C:21](=[CH:22][C:23](B(O)O)=[CH:24][CH:25]=2)[CH:20]=[CH:19]1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:1]12[CH2:9][CH:5]([CH2:6][CH2:7][CH2:8]1)[CH:4]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:23]3[CH:22]=[C:21]4[C:26](=[CH:25][CH:24]=3)[NH:18][CH:19]=[CH:20]4)=[CH:13][N:12]=1)[CH2:3][CH2:2]2

Participants

4

Reactant 2

HCID 27343615-Indolylboronic acidHCID 67377634HCID 67377634, compound

Product 1

HCID 16755225HCID 16755225, compoundYield 43.9%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A microwave vial containing a stirring bar is loaded with 148 mg (0.5 mmol) of (4SR, 5RS)-(1-aza-bicyclo[3.3.1]non-4-yl)-(5-bromo-pyridin-2-yl)-amine, 98 mg (0.61 mmol) of indole-5-boronic acid and 29.7 mg of tetrakis(triphenylphosphine)palladium, capped and after evacuation purged with argon. After addition of 9 ml of toluene, 1 ml of EtOH and 1 ml of 21 M Na2CO3 soln. the mixture is irradiated at 120° C. for 45 min in a microwave reactor (Initiator Exp, Biotage). The reaction mixture is filtered over hyflo and diluted with AcOEt. The aq. phase is extracted with AcOEt, the combined organic phases are washed with water and brine, dried over Na2 SO4 and evaporated. The residue is purified by medium pressure chromatography on silica gel with AcOEt/MeOH/NEt3 50:45:5 affording a foam which after trituration with pentane yields 73 mg of (4SR,5RS)-(1-aza-bicyclo[3.3.1]non-4-yl)-[5-(1H-indol-5-yl]-pyridin-2-yl)-amine as beige powder. MS (ES+): m/e=333 (MH+).

Workup

  1. additionA microwave vial containing a stirring bar
  2. customcapped
  3. customafter evacuation purged with argon
  4. additionAfter addition of 9 ml of toluene, 1 ml of EtOH and 1 ml of 21 M Na2CO3 soln
  5. customthe mixture is irradiated at 120° C. for 45 min in a microwave reactor (Initiator Exp, Biotage)
  6. filtrationThe reaction mixture is filtered over hyflo
  7. additiondiluted with AcOEt
  8. extractionThe aq. phase is extracted with AcOEt
  9. washthe combined organic phases are washed with water and brine
  10. customdried over Na2 SO4
  11. customevaporated
  12. customThe residue is purified by medium pressure chromatography on silica gel with AcOEt/MeOH/NEt3 50:45:5 affording a foam which after trituration with pentane

Sources & evidence

ORD record
ord-c44c0114876746f18ec4b6adf9e656f0
Source dataset
uspto-grants-2014_06
Patent number
US08759346B2

Reaction notes

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