Sodium Carbonate → HCID 60197473, compound

HRID 2169635Notes

Reaction equation

HRID 2169635 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([NH:15][CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:14])[CH2:7][C@@H:6]3[CH2:23][O:24][CH2:25][CH2:26][N:5]3[C:4]=2[N:3]=1.[OH:27][CH2:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.CCOC(C)=O>[OH:27][CH2:28][C:29]1[CH:34]=[C:33]([C:2]2[N:11]=[CH:10][C:9]3[N:8]([CH2:12][C:13]([NH:15][CH2:16][CH:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[O:14])[CH2:7][C@@H:6]4[CH2:23][O:24][CH2:25][CH2:26][N:5]4[C:4]=3[N:3]=2)[CH:32]=[CH:31][CH:30]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 86670145HCID 86670145, compound

Product 1

HCID 60197473HCID 60197473, compoundYield 79.4%

Reagents, catalysts & solvents 3

HCID 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-((tetrahydro-2H-pyran-4-yl)methyl)acetamide (PREPARATION x26, 50 mg, 0.131 mmol), 3-(hydroxymethyl)phenylboronic acid (29.8 mg, 0.196 mmol), tetrakis(triphenylphospine)palladium(0) (15.13 mg, 0.013 mmol) and sodium carbonate (27.8 mg, 0.262 mmol) in 1,4-dioxane (0.5 mL) and H2O (0.25 mL) was heated to 120° C. in a microwave for 1 hour. 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 (amine-functionalized silica, 0-10% MeOH gradient in CHCl3) to afford the title compound as an off-white solid (47.2 mg, 0.104 mmol, 79%). 1H NMR (400 MHz, DMSO-d6) δ 1.06-1.24 (m, 2 H), 1.47-1.71 (m, 3 H), 2.92-3.03 (m, 3 H), 3.12-3.37 (m, 5 H), 3.50-3.67 (m, 2 H), 3.73-3.93 (m, 4 H), 3.98-4.07 (m, 2 H), 4.50-4.60 (m, 3 H), 5.21 (t, J=5.81 Hz, 1 H), 7.26-7.38 (m, 2 H), 7.50 (s, 1 H), 8.06-8.11 (m, 2 H), 8.18 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C24H31N5O4, 453.24; found 454.4.

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 (amine-functionalized silica, 0-10% MeOH gradient in CHCl3)

Sources & evidence

ORD record
ord-814f91e8227041ef9fdaf2261e579496
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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