1H-Indole-4-boronic acid → HCID 60197266, compound

HRID 2169654Notes

Reaction equation

HRID 2169654 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]3[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:14]=3[C:15]([NH2:17])=[O:16])[CH2:7][CH:6]3[CH2:23][O:24][CH2:25][CH2:26][N:5]3[C:4]=2[N:3]=1.[NH:27]1[C:35]2[C:30](=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=2)[CH:29]=[CH:28]1>O1CCOCC1.C([O-])(O)=O.[Na+].CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH:27]1[C:35]2[C:30](=[C:31]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH2:12][C:13]5[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:14]=5[C:15]([NH2:17])=[O:16])[CH2:7][CH:6]5[CH2:23][O:24][CH2:25][CH2:26][N:5]5[C:4]=4[N:3]=3)[CH:32]=[CH:33][CH:34]=2)[CH:29]=[CH:28]1

Participants

7

Reactant 2

HCID 27631731H-Indole-4-boronic acidHCID 86670151HCID 86670151, compound

Product 1

HCID 60197266HCID 60197266, compoundYield 33.3%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

To a 10 mL vial were added 2-((2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)methyl)-4-methylbenzamide (PREPARATION x84, 57 mg, 0.152 mmol), 1H-indol-4-ylboronic acid (49.1 mg, 0.305 mmol), and PdCl2(dppf) (11.16 mg, 0.015 mmol) in dioxane (2 mL) and saturated NaHCO3 (0.4 mL). The resulting orange suspension was heated to 100° C. and stirred overnight. The reaction mixture was subsequently diluted with EtOAc and washed with saturated NH4Cl (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The product was purified by preparative HPLC, using a 20-45% CH3CN gradient in H2O (with 0.05% TFA). The pure fractions were combined and lyophilized to give the title compound as a yellow solid (23 mg, 33%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.33 (s, 3 H), 3.06-3.19 (m, 1 H), 3.24-3.33 (m, 2 H), 3.56-3.64 (m, 1 H), 3.89-4.05 (m, 1 H), 4.06-4.18 (m, 1 H), 4.41-4.55 (m, 1 H), 4.67-4.81 (m, 2 H), 6.94-7.08 (m, 1 H), 7.21-7.33 (m, 2 H), 7.33-7.41 (m, 1 H), 7.44-7.54 (m, 1 H), 7.54-7.74 (m, 2 H), 7.79-7.91 (m, 1 H), 11.46-11.66 (m, 1H); ESI-MS m/z [M+H]′ calc'd for C26H26N6O2, 455.2; found 455.3.

Workup

  1. washwashed with saturated NH4Cl (3×)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-0445279e400e4acbb38074ab99b0e4b3
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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