Sodium Carbonate → 5-(6-Morpholino-1,5-naphthyridin-3-yl)benzo[d]oxazol-2-amine

HRID 2199911Notes

Reaction equation

HRID 2199911 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[N:9]2)=[N:4][CH:3]=1.[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:15]1[CH2:16][CH2:17][N:12]([C:8]2[N:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[N:4]=[CH:3][C:2]([C:25]2[CH:26]=[CH:27][C:21]4[O:20][C:19]([NH2:18])=[N:23][C:22]=4[CH:24]=2)=[CH:11]3)[CH2:13][CH2:14]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 461995742-Aminobenzo[d]oxazol-5-ylboronic acidHCID 679930577-Bromo-2-morpholino-1,5-naphthyridine

Product 1

HCID 546753025-(6-Morpholino-1,5-naphthyridin-3-yl)benzo[d]oxazol-2-amineYield 67.2%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 7-bromo-2-morpholino-1,5-naphthyridine (F-32) (180 mg, 0.6 mmol, 1.0 eq), 2-aminobenzo[d]oxazol-5-ylboronic acid (131 mg, 0.73 mmol, 1.2 eq), Pd(PPh3)4 (71 mg, 0.06 mmol, 0.1 eq), and Na2CO3 (195 mg, 1.8 mmol, 3.0 eq) were dissolved in a mixture of 1,4-dioxane (10 mL) and water (10 mL). The resulting mixture was degassed and back-filled with argon three times and heated at reflux under an argon atmosphere for 2 h. The reaction was complete based on TLC analysis. The mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (3-5% MeOH-DCM) to afford 5-(6-morpholino-1,5-naphthyridin-3-yl)benzo[d]oxazol-2-amine (73) (140 mg, 67.2% yield). 1H NMR (400 MHz, DMSO-d6) δ: 8.93 (s, 1H), 8.10 (m, 2H), 7.66 (s, 1H), 7.53 (s, 2H), 7.45 (m, 3H), 3.74 (m, 8H); ESI-MS m/z: 348.11 [M+H]1.

Workup

  1. customThe resulting mixture was degassed
  2. additionback-filled with argon three times
  3. temperatureheated
  4. temperatureat reflux under an argon atmosphere for 2 h
  5. concentrationThe mixture was concentrated in vacuo
  6. customthe residue was purified by column chromatography on silica gel (3-5% MeOH-DCM)

Sources & evidence

ORD record
ord-899acb8269054441bd9fbded0fae066f
Source dataset
uspto-grants-2016_06
Patent number
US09359352B2

Reaction notes

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