4-Chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridine → 4-(3-methyl-2-(2-pyridinyl)-1,8-naphthyridin-4-yl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzoxazine

HRID 1618734Notes

Reaction equation

HRID 1618734 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:16]=[CH:15][C:10]3[O:11][CH2:12][CH2:13][NH:14][C:9]=3[CH:8]=2)[CH2:3][CH2:2]1.Cl[C:18]1[C:27]2[C:22](=[N:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)[C:19]=1[CH3:34]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].C1(C)C=CC=CC=1>[CH3:34][C:19]1[C:20]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[N:21][C:22]2[C:27]([C:18]=1[N:14]1[C:9]3[CH:8]=[C:7]([N:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)[CH:16]=[CH:15][C:10]=3[O:11][CH2:12][CH2:13]1)=[CH:26][CH:25]=[CH:24][N:23]=2

Participants

5

Reactant 2

HCID 596310684-Chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridineHCID 67285003HCID 67285003, compound

Product 1

HCID 672852504-(3-methyl-2-(2-pyridinyl)-1,8-naphthyridin-4-yl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzoxazine

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by using 6-morpholino-3,4-dihydro-2H-benzo-[b][1,4]oxazine (68 mg, 0.31 mmol), 4-chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridine (79 mg, 0.31 mmol), XPhos precatalyst (23 mg, 0.031 mmol) in toluene (5 mL) for 2 h at 100° C. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 4-(3-methyl-2-(2-pyridinyl)-1,8-naphthyridin-4-yl)-6-(4-morpholinyl)-3,4-dihydro-2H-1,4-benzoxazine. 1H NMR (400 MHz, chloroform-d) δ ppm 9.10 (1H, dd, J=4.1, 2.0 Hz), 8.71 (1H, ddd, J=4.8, 1.9, 1.0 Hz), 8.16-8.24 (2H, m), 7.92 (1H, td, J=7.7, 1.8 Hz), 7.37-7.45 (2H, m), 6.89 (1H, d, J=8.8 Hz), 6.31 (1H, dd, J=8.8, 2.7 Hz), 5.60 (1H, d, J=2.7 Hz), 4.42-4.52 (2H, m), 3.80-3.87 (1H, m), 3.62-3.76 (5H, m), 2.68-2.80 (4H, m), 2.53 (3H, s). Mass Spectrum (ESI) m/e=440.0 (M+1).

Workup

  1. customPrepared
  2. customfor 2 h
  3. customat 100° C
  4. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-f0028bcfe7c545b8bbcc32b058fd7e29
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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