1H-Indole-4-boronic acid → HCID 68195323, compound

HRID 2169605Notes

Reaction equation

HRID 2169605 reaction equation
[C:1]([O:4][C:5]([CH3:25])([CH2:7][CH2:8][CH2:9][N:10]1[CH2:19][C@@H:18]2[CH2:20][O:21][CH2:22][CH2:23][N:17]2[C:16]2[N:15]=[C:14](Cl)[N:13]=[CH:12][C:11]1=2)[CH3:6])(=[O:3])[CH3:2].[NH:26]1[C:34]2[CH:33]=[CH:32][CH:31]=[C:30](B(O)O)[C:29]=2[CH:28]=[CH:27]1>Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:1]([O:4][C:5]([CH3:25])([CH2:7][CH2:8][CH2:9][N:10]1[CH2:19][C@@H:18]2[CH2:20][O:21][CH2:22][CH2:23][N:17]2[C:16]2[N:15]=[C:14]([C:30]3[CH:31]=[CH:32][CH:33]=[C:34]4[C:29]=3[CH:28]=[CH:27][NH:26]4)[N:13]=[CH:12][C:11]1=2)[CH3:6])(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 27631731H-Indole-4-boronic acidHCID 86670148HCID 86670148, compound

Product 1

HCID 68195323HCID 68195323, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
120 °C

Procedure

To a 2 mL microwave vial were added (R)-5-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-2-methylpentan-2-yl acetate (PREPARATION x81, 148 mg, 0.401 mmol), indole-4-boronic acid (64.6 mg, 0.401 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (16.50 mg, 0.020 mmol). The vial was evacuated and filled with nitrogen. After sealing the vial, dioxane (1600 μL) and saturated NaHCO3 (400 μL) were added. The mixture was then heated in a microwave to 120° C. for 45 minutes. After the mixture was cooled to room temperature, ACN (4 mL) was added and the mixture was filtered by syringe filter. The crude product was purified by preparatory HPLC using a gradient of 20-40% CH3CN (with 0.035% TFA) in H2O (with 0.05% TFA). The collected fractions were pooled, neutralized with NaHCO3, concentrated, and extracted with EtOAc. The combined organics were dried over MgSO4, filtered, and concentrated to give the title compound (48 mg, 27%). ESI-MS m/z [M+H]+ calc'd for C25H31N5O3, 450.25; found 450.3.

Workup

  1. customThe vial was evacuated
  2. additionfilled with nitrogen
  3. additionwere added
  4. temperatureAfter the mixture was cooled to room temperature
  5. additionACN (4 mL) was added
  6. filtrationthe mixture was filtered by syringe
  7. filtrationfilter
  8. customThe crude product was purified by preparatory HPLC
  9. concentrationconcentrated
  10. extractionextracted with EtOAc
  11. dry with materialThe combined organics were dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-3268ea5b3e5a4f4fbb773248891d3315
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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