Potassium Carbonate → isopropyl 4-(4-(4-cyano-2-fluorophenoxy)-6H-pyrimido[5,4-b][1,4]oxazin-8(7H)-yl)piperidine-1-carboxylate

HRID 604350Notes

Reaction equation

Cl[C:2]1[C:7]2[O:8][CH2:9][CH2:10][N:11]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][CH:21]([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[C:6]=2[N:5]=[CH:4][N:3]=1.[F:24][C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][C:32]=1[OH:33])[C:28]#[N:29].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CO>[C:28]([C:27]1[CH:30]=[CH:31][C:32]([O:33][C:2]2[C:7]3[O:8][CH2:9][CH2:10][N:11]([CH:12]4[CH2:17][CH2:16][N:15]([C:18]([O:20][CH:21]([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]4)[C:6]=3[N:5]=[CH:4][N:3]=2)=[C:25]([F:24])[CH:26]=1)#[N:29]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of isopropyl 4-(4-chloro-6H-pyrimido[5,4-b][1,4]oxazin-8(7H)-yl)piperidine-1-carboxylate from Example 20A (10.0 mg, 0.029 mmol) and 3-fluoro-4-hydroxybenzonitrile (12.07 mg, 0.088 mmol) in DMF (0.4 mL) was added K2CO3 (12.17 mg, 0.088 mmol). The reaction mixture was stirred in a sealed vial for 3 days at 120° C. The reaction mixture was cooled to RT. The reaction mixture was diluted with MeOH, filtered and purified by reverse phase HPLC (H2O/CH3CN) to give isopropyl 4-(4-(4-cyano-2-fluorophenoxy)-6H-pyrimido[5,4-b][1,4]oxazin-8(7H)-yl)piperidine-1-carboxylate (1.0 mg, 2.265 μmol, 7.72% yield) as Example 148 as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.27 (d, J=6.05 Hz, 6H) 1.55-1.79 (m, 4H) 2.85-2.95 (m, 2H) 3.44-3.54 (m, 2H) 4.05-4.15 (m, 2H) 4.24-4.35 (m, 2H) 4.84-4.95 (m, 2H) 7.29-7.40 (m, 1H) 7.45-7.52 (m, 2H) 7.88 (s, 1H). LRMS (ESI): 442.5 [M+H]+.

Workup

temperatureThe reaction mixture was cooled to RT
filtrationfiltered
custompurified by reverse phase HPLC (H2O/CH3CN)

Sources & evidence

ORD record: ord-c41da36e077942c6b13272054a48697d
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07910583B2

Reaction notes

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