Cesium carbonate → Isopropyl 4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

HRID 1518476Notes

Reaction equation

HRID 1518476 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25](C)([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)=[CH:11][C:10]2=[O:29])=[C:5]([F:30])[CH:4]=1)#[N:2].O=C1C=C(OC2CCN(C(OC(C)(C)C)=O)CC2)C=CN1C1C=NC=CC=1.ClC1N=CC(CCC)=CN=1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][CH:25]([CH3:26])[CH3:27])=[O:23])[CH2:18][CH2:17]3)=[CH:11][C:10]2=[O:29])=[C:5]([F:30])[CH:4]=1)#[N:2]

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 27357842-Chloro-5-propylpyrimidineHCID 57468410Tert-butyl 4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateHCID 67367446Tert-butyl 4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Product 1

HCID 57468421Isopropyl 4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Procedure

Example 188 was prepared according to procedures described in Example 132 substituting tert-butyl 4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (Example 176) for tert-butyl 4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate in Step C and substituting isopropyl carbonochloridate (1 Molar in Toluene, Aldrich) for 2-chloro-5-propylpyrimidine and substituting triethyl amine for cesium carbonate in Step D except that reaction was stirred at room temperature for 20 min and then washed with HCl solution (1 Molar in H2O). The crude solid was purified by flash chromatography (SiO2, 0 to 100% EtOAc in CH2Cl2). 1H NMR (500 MHz, CDCl3) δ ppm 7.49-7.58 (m, 3 H), 7.08 (d, J=7.70 Hz, 1 H), 6.02 (dd, J=7.70, 2.20 Hz, 1 H), 5.93 (d, J=2.20 Hz, 1 H), 4.87-4.95 (m, 1 H), 4.45-4.49 (m, 1 H), 3.69-3.77 (m, 2 H), 3.32-3.39 (m, 2 H), 1.92-2.00 (m, 2 H), 1.72-1.81 (m, 2 H), 1.24 (d, J=6.60 Hz, 6 H). MS (ESI) 400 (M+H).

Workup

  1. customExample 188 was prepared
  2. washwashed with HCl solution (1 Molar in H2O)
  3. customThe crude solid was purified by flash chromatography (SiO2, 0 to 100% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-93e0c57c12f64c18822317ba2b281837
Source dataset
uspto-grants-2012_07
Patent number
US08232404B2

Reaction notes

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