Reaction SMILES: [NH2:1][C:2]1[C:7](=[O:8])[NH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:18][CH2:17][CH2:16]3)=[CH:11][CH:10]=2)=[C:4]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:3]=1.CCN(C(C)C)C(C)C.[Cl-].Br[CH:44]([CH2:47][CH2:48]Br)[CH2:45][OH:46].C(=O)(O)[O-:51].[Na+]>C1COCC1>[OH:46][CH2:45][CH2:44][CH:47]1[O:8][C:7]2[N:6]=[C:5]([C:9]3[CH:10]=[CH:11][C:12]([C:15]4([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:18][CH2:17][CH2:16]4)=[CH:13][CH:14]=3)[C:4]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:3][C:2]=2[NH:1][C:48]1=[O:51].[C:27]1([C:4]2[C:5]([C:9]3[CH:10]=[CH:11][C:12]([C:15]4([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:18][CH2:17][CH2:16]4)=[CH:13][CH:14]=3)=[N:6][C:7]3[O:8][CH:44]4[CH2:47][CH2:48][O:46][C:45]4=[N:1][C:2]=3[CH:3]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3[nH]c(=O)c(N)cc3-c3ccccc3)cc2)CCC1
Reactant: O=C([O-])O
Reactant: OCC(Br)CCBr
Agent: [Cl-]
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)N=C3OCCC3O4)cc2)CCC1
Product: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)NC(=O)C(CCO)O4)cc2)CCC1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
In a 100 mL round bottom flask was added tert-butyl 1-(4-(5-amino-6-oxo-3-phenyl-1,6-dihydropyridin-2-yl)phenyl)cyclobutylcarbamate (0.5 g, 1.159 mmol) in THF (Volume: 25 ml) to give a red suspension followed with the addition of DIPEA (1.0 ml). 2,4-dibromobutanol chloride (0.735 g, 2.78 mmol) in THF (5 ml) was added in drop wise at 0 degree. The resulted mixture was stirred at room temperature for 20 hours. The reaction mixture was transferred to a 250 ml round bottom flask and sodium bicarbonate saturated solution (40 ml) and sodium bicarbonate (1 g) was added. The resulted mixture was heated to reflux for 24 h. The reaction mixture was cooled down to room temperature. The organic phase was separated. The aqueous phase was extracted with ethyl acetate (45 ml). The organic phases were combined and washed with water (30 mlX2), brine (25 ml) then concentrated at reduced pressure. The residue was suspended in DCM (10 ml). The precipitate was collected by filtration and washed with DCM (5 ml) to afford crude product which was purified by biotage column (25 g silicon) to afford tert-butyl 1-(4-(3-(2-hydroxyethyl)-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (45 mg) and tert-butyl 1-(4-(7-phenyl-3,3a-dihydro-2H-furo[2,3-e]pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (0.35 g). 1H NMR (500 MHz, CD3OD): 7.50 (s, 1H), 7.31 (m, 2H), 7.26 (m, 5H), 7.16 (m, 2H), 5.38 (dd, 1H), 4.72 (t, 1H), 4.55 (m, 1H), 2.92 (m, 1H), 2.67 (m, 1H), 2.43-2.47 (m, 4H), 2.07 (m, 1H), 1.85 (m, 1H), 1.23-1.39 (br, 9H). LCMS (Method A): RT=6.89 min, M+H+=498.12. A solution of tert-butyl 1-(4-(7-phenyl-3,3a-dihydro-2H-furo[2,3-e]pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (0.35 g, 0.703 mmol) in DCM (15 ml) and acetic acid (10 ml) was stirred at room temp for 48 h. The reaction mixture was concentrated and portioned between ethyl acetate (40 ml) and water (30 ml). The separated organic phase was washed with water (2×25 ml), brine and concentrated to give product 0.36 g (45 mg). 1H NMR (500 MHz, CD3OD): 7.23-7.31 (m, 8H), 7.16 (m, 2H), 5.05 (dd, 1H), 3.91 (m, 1H), 3.85 (m, 1H), 2.45 (m, 4H), 2.26 (m, 1H), 2.15 (m, 1H), 2.07 (m, 1H), 1.86 (m, 1H), 1.23-1.39 (br, 9H). LCMS (Method A): RT=5.92 min, M+H+=516.04.