Sodium Carbonate → Tert-butyl(1-(4-(6-(2-aminobenzo[d]oxazol-5-yl)-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamate

HRID 2199900Notes

Reaction equation

HRID 2199900 reaction equation
[C:1]([O:5][C:6](=[O:30])[NH:7][C:8]([CH3:29])([CH3:28])[C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:18]=[N:19][C:20]3[C:25]([CH:26]=2)=[N:24][C:23](Cl)=[CH:22][CH:21]=3)[CH2:13][CH2:12]1)=[O:10])([CH3:4])([CH3:3])[CH3:2].[NH2:31][C:32]1[O:33][C:34]2[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][C:35]=2[N:36]=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>[C:1]([O:5][C:6](=[O:30])[NH:7][C:8]([CH3:29])([CH3:28])[C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:18]=[N:19][C:20]3[C:25]([CH:26]=2)=[N:24][C:23]([C:38]2[CH:39]=[CH:40][C:34]4[O:33][C:32]([NH2:31])=[N:36][C:35]=4[CH:37]=2)=[CH:22][CH:21]=3)[CH2:13][CH2:12]1)=[O:10])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 461995742-Aminobenzo[d]oxazol-5-ylboronic acidHCID 88874322Tert-butyl(1-(4-(6-chloro-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamate

Product 1

HCID 70648853Tert-butyl(1-(4-(6-(2-aminobenzo[d]oxazol-5-yl)-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamateYield 37.2%

Reagents, catalysts & solvents 3

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

Procedure

Tert-butyl(1-(4-(6-chloro-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamate (20) (190 mg, 0.44 mmol, 1.0 eq) and (2-aminobenzo[d]oxazol-5-yl)boronic acid (94 mg, 0.53 mmol, 1.2 eq) were dissolved in a mixture of 1,4-dioxane (10 mL) and water (10 mL). To this mixture, Pd(PPh3)4 (51 mg, 0.044 mmol, 0.1 eq) and sodium carbonate (140 mg, 1.32 mmol, 3.0 eq) were added sequentially. The resulting mixture was heated at reflux for 2 h with stirring under an argon atmosphere. The reaction was complete based on TLC analysis. The reaction mixture was concentrate in vacuo, and purified by silica gel column chromatography (1-5% MeOH—CH2Cl2) to afford the desired product, tert-butyl(1-(4-(6-(2-aminobenzo[d]oxazol-5-yl)-1,5-naphthyridin-3-yl)piperazin-1-yl)-2-methyl-1-oxopropan-2-yl)carbamate (D-21) (87 mg, 37.2%) as a yellow solid. ESI-MS m/z: 532.22[M+H]+.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 2 h
  3. concentrationThe reaction mixture was concentrate in vacuo
  4. custompurified by silica gel column chromatography (1-5% MeOH—CH2Cl2)

Sources & evidence

ORD record
ord-e10cb27691e645eca31377e61ccc583e
Source dataset
uspto-grants-2016_06
Patent number
US09359352B2

Reaction notes

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