Sodium Carbonate → 5-(3-Morpholinopyrido[2,3-b]pyrazin-6-yl)benzo[d]oxazol-2-amine

HRID 2199908Notes

Reaction equation

HRID 2199908 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:6]([N:17]=1)=[N:7][C:8]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)=[CH:9][N:10]=2.[NH2:18][C:19]1[O:20][C:21]2[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][C:22]=2[N:23]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[O:14]1[CH2:15][CH2:16][N:11]([C:8]2[N:7]=[C:6]3[N:17]=[C:2]([C:25]4[CH:26]=[CH:27][C:21]5[O:20][C:19]([NH2:18])=[N:23][C:22]=5[CH:24]=4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)[CH2:12][CH2:13]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 461995742-Aminobenzo[d]oxazol-5-ylboronic acidHCID 866975646-Chloro-3-morpholinopyrido[2,3-b]pyrazine

Product 1

HCID 546753435-(3-Morpholinopyrido[2,3-b]pyrazin-6-yl)benzo[d]oxazol-2-amineYield 72%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloro-3-morpholinopyrido[2,3-b]pyrazine (E-29) (100 mg, 0.4 mmol, 1.0 eq), 2-aminobenzo[d]oxazol-5-ylboronic acid (108 mg, 0.6 mmol, 1.5 eq), Pd(PPh3)4 (50 mg, 0.04 mmol, 0.1 eq), and Na2CO3 (0.22 g, 2.0 mmol, 5.0 eq),) were dissolved in a mixture of 1,4-dioxane (15 mL) and water (5 mL). The resulting mixture was degassed and back-filled with argon three times and heated at reflux temperature for 2 h. The reaction was complete based on TLC analysis. The reaction mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (60:1:0.02 MeOH-DCM-NH3.H2O) to afford 5-(3-morpholinopyrido[2,3-b]pyrazin-6-yl)benzo[d]oxazol-2-amine (2) (100 mg, 72% yield) as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ: 8.86 (s, 1H), 8.26 (m, 1H), 8.06 (m, 2H), 7.92 (m, 1H), 7.55 (bs, 2H), 7.47 (m, 1H), 3.82 (m, 8H); ESI-MS m/z: 349.14 [M+H]+.

Workup

  1. customThe resulting mixture was degassed
  2. additionback-filled with argon three times
  3. temperatureheated
  4. temperatureat reflux temperature for 2 h
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customthe residue was purified by column chromatography on silica gel (60:1:0.02 MeOH-DCM-NH3.H2O)

Sources & evidence

ORD record
ord-1a21ee0aecee4b35bf65c938c247af4b
Source dataset
uspto-grants-2016_06
Patent number
US09359352B2

Reaction notes

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