1H-Indole-4-boronic acid → HCID 68195053, compound

HRID 1631806Notes

Reaction equation

HRID 1631806 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([C@H:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[CH3:13])[C:7](=[O:21])[C@@H:6]3[CH2:22][O:23][CH2:24][CH2:25][N:5]3[C:4]=2[N:3]=1.[NH:26]1[C:34]2[C:29](=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=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]>[Cl:20][C:17]1[CH:16]=[CH:15][C:14]([C@@H:12]([N:8]2[C:7](=[O:21])[CH:6]3[CH2:22][O:23][CH2:24][CH2:25][N:5]3[C:4]3[N:3]=[C:2]([C:30]4[CH:31]=[CH:32][CH:33]=[C:34]5[C:29]=4[CH:28]=[CH:27][NH:26]5)[N:11]=[CH:10][C:9]2=3)[CH3:13])=[CH:19][CH:18]=1

Participants

4

Reactant 2

HCID 27631731H-Indole-4-boronic acidHCID 86670154HCID 86670154, compound

Product 1

HCID 68195053HCID 68195053, compoundYield 44.3%

Reagents, catalysts & solvents 1

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

Procedure

The title compound was prepared in a manner similar to EXAMPLE 85 using (S)-2-chloro-5-((S)-1-(4-chlorophenyl)ethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (43 mg, 0.113 mmol), 1H-indol-4-ylboronic acid (36.5 mg, 0.227 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (4.66 mg, 5.67 μmol). The crude product was purified by preparatory HPLC using a gradient of 35-50% CH3CN (with 0.035% TFA) in H2O (with 0.05% TFA). Lyophilization of the collected fractions gave a diastereomeric mixture of title compound (TFA salt) as a yellow powder (23 mg, 44.1%). 1H NMR (400 MHz, DMSO-d6) δ 1.74-1.81 (m, 2H), 1.82-1.89 (m, 1H), 11.20-11.34 (m, 1H), 3.07-3.18 (m, 1H), 3.58-3.77 (m, 3H), 4.03-4.12 (m, 2H), 4.23-4.31 (m, 2H), 4.41-4.60 (m, 3H), 6.32-6.08 (m, 1H), 7.12-7.19 (m, 1H), 7.22-7.30 (m, 1H), 7.35-7.55 (m, 6H), 7.81-7.73 (m, 1H), 7.91-8.01 (m, 1H). ESI-MS m/z [M+H]+ calc'd for C25H22ClN5O2, 460.15. found 460.4.

Workup

  1. customThe crude product was purified by preparatory HPLC
  2. customLyophilization of the collected fractions gave

Sources & evidence

ORD record
ord-903fc8cc0bd641bf9569a02f5c574b87
Source dataset
uspto-grants-2014_07
Patent number
US08791107B2

Reaction notes

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