Sodium Carbonate → HCID 68195143, compound

HRID 2169652Notes

Reaction equation

HRID 2169652 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:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=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>[OH:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([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:31][CH:30]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 86670145HCID 86670145, compound

Product 1

HCID 68195143HCID 68195143, compoundYield 32%

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-((tetrahydro-2H-pyran-4-yl)methyl)acetamide (PREPARATION x26, 50 mg, 0.131 mmol), 4-(hydroxymethyl)phenylboronic acid (29.8 mg, 0.196 mmol), tetrakis(triphenylphosphine)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 water (0.25 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 a white solid, which was recrystallized from EtOH/EtOAc to give the title compound as an off-white solid (19.0 mg, 32.0%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02-1.21 (m, 2 H), 1.48-1.71 (m, 3 H), 2.91-3.02 (m, 3 H), 3.12-3.32 (m, 5 H), 3.50-3.67 (m, 2 H), 3.73-4.08 (m, 6 H), 4.49-4.61 (m, 3 H), 5.19 (t, J=5.68 Hz, 1 H), 7.34 (d, J=8.59 Hz, 2 H), 7.47-7.51 (m, 1 H), 8.08 (t, J=5.94 Hz, 1 H), 8.16 (d, J=8.34 Hz, 2 H); ESI-MS m/z [M+H]+ calc'd for C24H31N5O4, 454.24; 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 (silica-NH, gradient 0-10% MeOH/CHCl3)
  7. customto afford a white solid, which
  8. customwas recrystallized from EtOH/EtOAc

Sources & evidence

ORD record
ord-b30ce3b7e13041c7a332c7cc0b0947cf
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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