Sodium Carbonate → HCID 68195034, compound

HRID 2169650Notes

Reaction equation

HRID 2169650 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([N:15]([CH3:23])[CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:14])[CH2:7][C@@H:6]3[CH2:24][O:25][CH2:26][CH2:27][N:5]3[C:4]=2[N:3]=1.[NH:28]1[C:36]2[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[C:31]=2[CH:30]=[CH:29]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:28]1[C:36]2[C:31](=[C:32]([C:2]3[N:11]=[CH:10][C:9]4[N:8]([CH2:12][C:13]([N:15]([CH3:23])[CH2:16][CH:17]5[CH2:22][CH2:21][O:20][CH2:19][CH2:18]5)=[O:14])[CH2:7][C@@H:6]5[CH2:24][O:25][CH2:26][CH2:27][N:5]5[C:4]=4[N:3]=3)[CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27631731H-Indole-4-boronic acidHCID 86670144HCID 86670144, compound

Product 1

HCID 68195034HCID 68195034, compoundYield 43.7%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
120 °C

Procedure

A mixture of (R)-2-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-N-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide (PREPARATION x79, 70 mg, 0.177 mmol), indole-4-boronic acid (42.7 mg, 0.265 mmol), tetrakis(triphenylphosphine)palladium(0) (20.43 mg, 0.018 mmol), and sodium carbonate (37.5 mg, 0.354 mmol) in 1,4-dioxane (0.7 mL) and water (0.35 mL) was heated to 120° C. for 1 hour in a microwave. After cooling to room temperature, the reaction mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (silica-NH, gradient 0-10% MeOH/CHCl3) to afford the title compound as an off-white solid (36.8 mg, 43.7%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04-1.61 (m, 4 H), 1.78-1.97 (m, 1 H), 2.80-3.09 (m, 4 H), 3.12-3.38 (m, 7 H), 3.58 (t, J=9.98 Hz, 2 H), 3.78-4.16 (m, 5 H), 4.41-4.60 (m, 2 H), 7.11 (t, J=7.71 Hz, 1 H), 7.26-7.64 (m, 4 H), 7.86-7.95 (m, 1 H), 11.11 (br s, 1 H); ESI-MS m/z [M+H]+ calc'd for C26H32N6O3, 477.26; found 477.3.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (silica-NH, gradient 0-10% MeOH/CHCl3)

Sources & evidence

ORD record
ord-66f80354362f4847963ed477a36d8181
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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