Sodium Carbonate → HCID 68195353, compound

HRID 2169651Notes

Reaction equation

HRID 2169651 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C@H:6]3[CH2:20][O:21][CH2:22][CH2:23][N:5]3[C:4]=2[N:3]=1.[NH:24]1[C:32]2[CH:31]=[CH:30][CH:29]=[C:28](B(O)O)[C:27]=2[CH:26]=[CH:25]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.CCOC(C)=O.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>[NH:24]1[C:32]2[C:27](=[C:28]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C@H:6]5[CH2:20][O:21][CH2:22][CH2:23][N:5]5[C:4]=4[N:3]=3)[CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27631731H-Indole-4-boronic acidHCID 86670146HCID 86670146, compound

Product 1

HCID 68195353HCID 68195353, compoundYield 91%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-tert-butyl 2-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)acetate (PREPARATION x80, 100 mg, 0.293 mmol), indole-4-boronic acid (70.8 mg, 0.440 mmol), tetrakis(triphenylphosphine)palladium(0) (33.9 mg, 0.029 mmol), and sodium carbonate (62.2 mg, 0.587 mmol) in 1,4-dioxane (1 mL) and water (0.5 mL) was heated to 120° C. for 1 hour in a microwave. After cooling to room temperature, the reaction mixture was diluted with EtOAc, filtered through Celite, washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified via flash column chromatography (silica-NH, gradient 10-80% EtOAc/hexane) to afford the title compound as an off-white solid (112 mg, 91%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38-1.48 (m, 9 H), 2.98-3.09 (m, 1 H), 3.15-3.40 (m, 3 H), 3.52-3.64 (m, 2 H), 3.87-4.11 (m, 3 H), 4.28 (d, J=17.94 Hz, 1 H), 4.52-4.60 (m, 1 H), 7.12 (t, J=7.71 Hz, 1 H), 7.29-7.44 (m, 3 H), 7.51-7.68 (m, 1 H), 7.93 (dd, J=7.45, 0.88 Hz, 1 H), 11.12 (br s, 1 H); ESI-MS m/z [M+H]+ calc'd for C23H27N5O3, 422.22; found 422.3.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationfiltered through Celite
  3. washwashed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via flash column chromatography (silica-NH, gradient 10-80% EtOAc/hexane)

Sources & evidence

ORD record
ord-38996cbd113147eabcb25156de07a313
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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