Sodium Carbonate → 5-(7-(3-(4-Isopropylpiperazin-1-yl)azetidin-1-yl)-1,5-naphthyridin-2-yl)benzo[d]oxazol-2-amine

HRID 2199892Notes

Reaction equation

HRID 2199892 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([N:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]4)[CH2:13]3)=[CH:7][N:8]=2)[N:3]=1.[NH2:25][C:26]1[O:27][C:28]2[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][C:29]=2[N:30]=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>[CH:22]([N:19]1[CH2:20][CH2:21][N:16]([CH:14]2[CH2:15][N:12]([C:6]3[CH:5]=[C:4]4[C:9]([CH:10]=[CH:11][C:2]([C:32]5[CH:33]=[CH:34][C:28]6[O:27][C:26]([NH2:25])=[N:30][C:29]=6[CH:31]=5)=[N:3]4)=[N:8][CH:7]=3)[CH2:13]2)[CH2:17][CH2:18]1)([CH3:24])[CH3:23]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 461995742-Aminobenzo[d]oxazol-5-ylboronic acidHCID 866975552-Chloro-7-(3-(4-isopropylpiperazin-1-yl)azetidin-1-yl)-1,5-naphthyridine

Product 1

HCID 679930445-(7-(3-(4-Isopropylpiperazin-1-yl)azetidin-1-yl)-1,5-naphthyridin-2-yl)benzo[d]oxazol-2-amineYield 42.5%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 2-chloro-7-(3-(4-isopropylpiperazin-1-yl)azetidin-1-yl)-1,5-naphthyridine (C-10) (220 mg, 0.636 mmol, 1.0 eq), 2-aminobenzo[d]oxazol-5-ylboronic acid (135 mg, 0.763 mmol, 1.2 eq), Pd(PPh3)4 (73 mg, 0.06 mmol, 0.1 eq), and Na2CO3 (202 mg, 1.908 mmol, 3.0 eq) were dissolved in a mixture of 1,4-dioxane (30 mL) and water (9 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 (1:5 MeOH-DCM) to afford the desired product 5-(7-(3-(4-isopropylpiperazin-1-yl)azetidin-1-yl)-1,5-naphthyridin-2-yl)benzo[d]oxazol-2-amine (72) (120 mg, 42.5% yield). 1H NMR (300 MHz, DMSO-d6) δ: 8.35 (s, 1H), 8.20 (d, J=8.7 Hz, 1H), 8.02 (s, 1H), 7.98 (d, J=8.4 Hz, 1H), 7.87 (d, J=6.3 Hz, 1H), 7.48 (s, 2H), 7.42 (d, J=8.1 Hz, 1H), 7.08 (s, 1H), 4.12 (m, 2H), 3.85 (m, 2H), 3.36 (m, 1H), 3.23 (m, 4H), 2.47 (m, 1H), 2.37 (m, 4H), 0.95 (d, J=6.9 Hz, 6H); ESI-MS m/z: 444.21 [M+H]+.

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 (1:5 MeOH-DCM)

Sources & evidence

ORD record
ord-2b66db3695dd487db8b2e5dd2e5a76f5
Source dataset
uspto-grants-2016_06
Patent number
US09359352B2

Reaction notes

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